5 10 15 20 25 CA 03054001 2019-08-19 [description] [invention Title] ASYMMETRIC siRNA FOR INHIBITING EXPRESSION OF MALE PATTERN HAIR LOSS TARGET GENE [Technical Field] The present invention relates to asymmetric siRNA for inhibiting the expression of a target gene for male pattern hair loss and a use thereof, and more particularly to asymmetric siRNA for inhibiting the expression of the 3-oxo-5- alpha-steroid 4-dehydrogenase 1 (SRD5A1) gene, the 3-oxo-5- alpha-steroid 4-dehydrogenase 2 (SRD5A2) gene, or the androgen receptor (AR) gene, and a composition for preventing or treating hair loss which comprises the asymmetric siRNA. [Background Art] Human hair is formed in hair follicles. There are papillae in the hair follicles, small blood vessels are distributed in the papillae to supply nutrients necessary for hair growth, and sebaceous glands are distributed on the upper ends of side surfaces of the papillae to secrete sebum to protect the hair. The dermal papilla regulates hair growth and is the site where male hormones act in male-pattern hair loss. The hair matrix is a site where cell division occurs under the control of the dermal papilla and hair grows. 15 10 15 20 25 CA 03054001 2019-08-19 The main factor of male hair loss is due to the effect of abnormal hormones. At puberty, sex hormones are actively secreted and the secondary sexual character appears. These changes are caused by sex hormones, i.e., androgens (male hormones) and estrogens (female hormones). Androgens develop body hair under the eyebrows, and estrogen mainly promotes hair growth. For men, hair loss is due to excessive secretion of androgens which results in inhibition of the action of estrogen by the excessively secreted androgens. Specifically, steroid 5-alpha reductase is involved in the male hair loss mechanism by male hormones, and steroid 5- alpha reductase is a main enzyme that reduces testosterone, which is a male hormone, to DHT (dihydrotestosterone). The resulting DHT is known to bind to an androgen receptor to thereby regulate hair growth in the hair follicles and be involved in the proliferation of sebaceous glands. The androgen receptor is a male hormone (androgen) receptor and is known to be capable of binding to both testosterone and DHT, but have a stronger binding affinity with DHT. It is known that the inhibition of steroid 5-alpha reductase and an androgen receptor increases hair growth factors and induces hair growth, whereas the activation of steroid 5-alpha reductase and an androgen receptor inhibits hair growth, resulting in the occurrence of hair loss (Chhipa, RR et al., Prostate, 73:1483, 2013; Azzouni, F et al, 25 10 15 20 25 CA 03054001 2019-08-19 Advances in Urology, 2012:18, 2012; Winiarska, A. et al., Skin Pharmacology and Physiology, 19:311, 2006). There are two types of steroid 5-alpha reductase: type 1 and type 2. Steroid 5-alpha reductase type 1 is mainly distributed throughout the skin, especially in the sebaceous glands, and steroid 5-alpha reductase type 2 is mainly distributed around the dermal papilla of the hair follicles and in the outer root sheath. In the early stage of drug development, hair loss therapeutic agents targeting only steroid 5-alpha reductase type 2 have mainly been developed, but therapeutic agents for inhibiting both steroid 5-alpha reductase type 1 and type 2 have recently been developed since the type 1 also has been found to affect hair growth. Among these, finasteride may be used as a drug for inhibiting steroid 5-alpha reductase type 2. Finasteride was originally developed as a therapeutic agent for benign prostatic hypertrophy, it has been approved by the FDA and the Korean Food and Drug Administration as a male pattern hair loss therapeutic agent since finasteride was confirmed to promote hair growth in patients administered. Dutasteride is known to be a therapeutic ingredient that inhibits both steroid 5-alpha reductase type 1 and type 2. Drugs which bind to the androgen receptor and thus acts as an antagonist that hinders the binding between the androgen receptor and DHT are called anti-androgen drugs, and as these anti-androgen drugs, 35 10 15 20 25 CA 03054001 2019-08-19 Cimetidine, Spironolactone, Flutamide, Cyproterone acetate, and the like are known. However, these therapeutic ingredients have problems such as sexual dysfunction, fatigue appeal, and the like, and the use thereof is limited in women of childbearing age. These may cause fetal malformations when exposed to pregnant women. Therefore, there is a need to develop a therapeutic agent for hair loss without such side effects. Under these technical backgrounds, the inventors of the present invention confirmed that a novel RNAi drug with minimal side effects developed using siRNA for inhibiting the expression of the 3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1) gene, the 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2) gene, or the androgen receptor (AR) gene was able to exhibit a desired effect of preventing or treating hair loss, and thus completed the present invention. [Disclosure] [Technical Problem] It is an object of the present invention to provide asymmetric shorter duplex siRNA (asiRNA) specifically binding to a SRD5A1-encoding gene, a SRD5A2-encoding gene, or an ARencoding gene. It is another object of the present invention to provide a composition for preventing or treating hair loss which comprises the asiRNA, or a method of preventing or treating 45 10 15 20 25 CA 03054001 2019-08-19 hair loss. [Technical Solution] To achieve the above object, the present invention provides siRNA specifically binding to mRNA of a 3-oxo-5- alpha-steroid 4-dehydrogenase 1 (SRD5A1)-encoding gene, mRNA of a 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2)-encoding gene, or mRNA of an androgen receptor (AR)-encoding gene and comprising a sense strand having a length of 15-17 nt and an antisense strand complementary to the sense strand and having a length of 19 nt or more, wherein the 3'-terminus of the sense strand and the 5'-terminus of the antisense strand form a blunt end. The present invention also provides a composition for preventing or treating hair loss which comprises the siRNA. The present invention also provides a method of preventing or treating hair loss, comprising administering the siRNA to a subject. The present invention also provides a use of the siRNA for preventing or treating hair loss. The present invention also provides a use of the siRNA for preparing a drug for the prevention or treatment of hair loss. [Description of Drawings] 55 10 15 20 25 CA 03054001 2019-08-19 FIGS. 1A and IB illustrate results showing the gene inhibitory efficiency of asiRNA against 100 sequences targeting SRD5A1. HuH-7 cells were transfected with 0.3 nM asiRNA targeting each nucleotide sequence, and after 24 hours, the expression level of SRD5A1 mRNA was measured using qRTPCR, and the graphs show the mean and SD of two repeated experiments. FIG. 2 illustrates results showing the gene inhibitory efficiency of asiRNA against 12 sequences targeting SRD5A1. HuH-7 cells were transfected with 0.3 nM, 1 nM, or 10 nM asiRNA targeting each nucleotide sequence, and after 48 hours, the expression level of the SRD5A1 protein was measured by western blotting. FIG. 3 illustrates results showing the gene inhibitory efficiency of 12 kinds of cp-asiRNAs targeting SRD5A1 and having various chemical modifications added thereto, through two repeated experiments. HuH-7 cells were incubated with 1 pM or 3 pM cp-asiRNA targeting each nucleotide sequence, and after 48 hours, the expression level of the SRD5A1 protein was measured by western blotting. FIG. 4 illustrates results showing the gene inhibitory efficiency of 2 kinds of cp-asiRNA targeting SRD5A1 and having various chemical modifications added thereto. HuH-7 cells were incubated with 0.3pM, 1 pM, or 3 pM cp-asiRNA targeting each nucleotide sequence, and after 24 hours, the expression level 65 10 15 20 25 CA 03054001 2019-08-19 of SRD5A1 mRNA was measured using real-time PCR, and the graph shows the mean and SD of four repeated experiments. FIGS. 5A and 5B illustrate results showing the gene inhibitory efficiency of asiRNA against 112 sequences targeting SRD5A2. HuH-7 cells were transfected with 0.3 nM asiRNA targeting each nucleotide sequence, and after 24 hours, the expression level of SRD5A2 mRNA was measured using qRTPCR, and the graphs show the mean and SD of two repeated experiments. FIG. 6A illustrates results showing the gene inhibitory efficiency of asiRNA against 23 sequences targeting SRD5A2, and FIG. 6B illustrates results showing the gene inhibitory efficiency of asiRNA against 6 sequences and 4 sequences, which target SRD5A2. HuH-7 cells were transfected with 3 nM or 10 nM of asiRNA targeting each nucleotide sequence, and after 48 hours, the expression level of the SRD5A2 protein was measured by western blotting. FIG. 7 illustrates results showing the gene inhibitory efficiency of 12 kinds of cp-asiRNA targeting SRD5A2 and having various chemical modifications added thereto, through two repeated experiments. HuH-7 cells were incubated with 1 pM of cp-asiRNA targeting each nucleotide sequence, and after 48 hours, the expression level of the SRD5A2 protein was measured by western blotting. FIG. 8 illustrates results showing the gene inhibitory efficiency of 2 selected kinds of cp-asisRD5A2. HuH-7 cells 75 10 15 20 25 CA 03054001 2019-08-19 were incubated with cp-asiRNA targeting each nucleotide sequence at a concentration ranging from 1.95 nN to 1,000 nM, and after 24 hours, the expression level of SRD5A2 mRNA was measured by RT-PCR. FIG. 9 illustrates results showing the gene inhibitory efficiency of 2 selected kinds of cp-asiSRD5A2. HuH-7 cells were incubated with 0.1 pM, 0.3 pM, 1 pM, or 3 pM of cp-asiRNA targeting each nucleotide sequence, and after 48 hours, the expression level of the SRD5A2 protein was measured by western blotting. FIGS. 10A and 10B illustrate results showing the gene inhibitory efficiency of asiRNA against 118 sequences targeting AR. A549 cells were transfected with 0.3 nM of asiRNA targeting each nucleotide sequence, and after 24 hours, the expression level of AR mRNA was measured through qRT-PCR, the graphs showing the mean and SD of two repeated experiments. FIG. 11 illustrates results showing the inhibitory efficiency of asiRNA against 20 sequences targeting AR at a protein level. A549 cells were transfected with 0.3 nM asiRNA targeting each nucleotide sequence, and after 48 hours, the expression level of the AR protein was measured by western blotting, and experiments were repeated three times. FIG. 12 illustrates results showing the gene inhibitory efficiency of asiRNA against 9 sequences targeting AR. A549 cells were transfected with 0.1 nM asiRNA targeting each 85 10 15 20 25 CA 03054001 2019-08-19 nucleotide sequence, and after 48 hours, the expression levels of AR mRNA and the AR protein were measured by qRT-PCR and western blotting, respectively. FIG. 13 illustrates results showing the gene inhibitory efficiency of 9 kinds of cp-asiRNA targeting an AR and having various chemical modifications added thereto. A549 cells were incubated with 1 pM or 3 pM of cp-asiRNA targeting each nucleotide sequence, and after 48 hours, the expression level of AR mRNA was measured through real-time PCR, and the graph shows the mean and SD of four repeated experiments. FIG. 14 illustrates results showing the gene inhibitory efficiency of 9 kinds of cp-asiRNA targeting an AR and having various chemical modifications added thereto. A549 cells were incubated with 1 pM of cp-asiRNA targeting each nucleotide sequence, and after 48 hours, the expression level of the AR protein was measured using a western blotting assay. [Detailed Description and Exemplary Embodiments] Unless otherwise defined, all technical and scientific terms as used herein have the same meanings as those commonly understood by one of ordinary skill in the art to which the present invention pertains. Generally, the nomenclature used herein is well known and commonly used in the art. Accordingly, in one aspect, the present invention relates to siRNA specifically binding to mRNA of a 3-oxo-5- alpha-steroid 4-dehydrogenase 1 (SRD5A1)-encoding gene having 95 10 15 20 25 CA 03054001 2019-08-19 SEQ ID NO: 678, mRNA of a 3-oxo-5-alpha-steroid 4- dehydrogenase 2 (SRD5A2)-encoding gene having SEQ ID NO: 679, or mRNA of an androgen receptor (AR)-encoding gene having SEQ ID NO: 680 and comprising a sense strand having a length of 15-17 nt and an antisense strand complementary to the sense strand and having a length of 19 nt or more, wherein the 3'- terminus of the sense strand and the 5'-terminus of the antisense strand form a blunt end. The SRD5A1-encoding gene, which is a target gene for male pattern hair loss, for example, androgenetic alopecia, has mRNA Accession Number: NM_001047.3, NM_001324322.1, or NM_001324323.1, which respectively include sequences with SEQ ID: 669, SEQ ID NO: 670, and SEQ ID NO: 671. The SRD5A2- encoding gene has mRNA Accession Number: NM_000348.3 and includes a sequence having SEQ ID NO: 672. The AR-encoding gene has mRNA Accession Number: NM_001011645.2 and includes a sequence having SEQ ID NO: 673. In the present invention, siRNA is a concept including all substances having a general RNA interference (RNAi) action. RNAi is an intracellular mechanism for gene regulation that was first found in Caenorhabditis elegans in 1998, and as for the mechanism action, it is known that the antisense strand of a double-stranded RNA introduced into a cell complementarily binds to mRNA of a target gene to thereby induce the degradation of the target gene. In this regard, small interfering RNA (siRNA) is one of the methods of 105 10 15 20 25 CA 03054001 2019-08-19 inhibiting gene expression in vitro. siRNAs of 19-21 bp in length are theoretically capable of performing selective inhibition against almost all genes, and thus can be developed as therapeutic agents for various gene-related diseases such as cancer, viral infection, and the like, and is the new candidate drug development technology that has recently drawn the most attention. The first attempt to perform in vivo treatment using siRNA in mammals was in mid-2003, and since then, there have been numerous reports of in vivo treatment thanks to many attempts for application studies. However, contrary to the possibility of in vivo treatment, side effects and disadvantages of siRNA have continually been reported. To develop an RNAi-based therapeutic agent, challenges such as: 1) the absence of an effective delivery system; 2) the off-target effect; 3) the induction of immune responses; and 4) intracellular RNAi mechanism saturation need to be overcome. Although siRNAs are an effective method of directly regulating target gene expression, it is difficult to develop a therapeutic agent using such siRNAs due to the above-described problems. With regard thereto, the applicant of the present invention has developed an asymmetric shorter duplex siRNA (asiRNA) structure-related technology (WO2009/078685). asiRNA is an asymmetric RNAi-inducing structure having a shorter double helix length than the 19+2 structure of existing siRNAs. asiRNA is a technology that has overcome known problems with 115 10 15 20 25 CA 03054001 2019-08-19 the existing siRNA structure technology, such as the offtarget effect, RNAi mechanism saturation, immune responses by TLR3 , and the like, and accordingly is used for the development of a new RNAi drug with minimal side effects. Based on this, the present invention provides asymmetric siRNA including a sense strand having a length of 15-17 nt and an antisense strand complementary to the sense strand and having a length of 19 nt or more, and thus the siRNA according to the present invention may stably maintain high delivery efficiency without incurring problems such as the off-target effect, RNAi mechanism saturation, immune responses by TLR3, and the like, and may inhibit the expression of a 5a-reductase type 1 target gene, a 5a-reductase type 2 target gene, and an androgen receptor target gene. In the present invention, the term "sense strand" refers to a polynucleotide having the same nucleic acid sequence as that of the SRD5A1-, SRD5A2-, or AR-encoding gene, and has a length of 15-17 nt. In one embodiment, the sense strand may have a length of 15 nt, 16 nt, or 17 nt. The inventors of the present application selected, as target genes, 5a-reductase type 1, 5a-reductase type 2, and an androgen receptor, which play a major role in inhibiting the synthesis of proteins required for hair follicle growth in male pattern hair loss and inducing hair loss by reducing the dermal papilla. As a result of screening 100 or more siRNAs targeting each target gene and selecting siRNAs with excellent 125 10 15 20 25 CA 03054001 2019-08-19 inhibitory efficiency from among the same, it was confirmed that siRNA comprising a sense strand having one selected from complementary to the sense strand, effectively reduced the expression of mRNA of the SRD5A1-, SRD5A2-, or AR-encoding SEQ ID NOS: 5, 6, 15, 18, 40, 48, 49, 59, 62, 69, 77, 86, 205, 208, 228, 231, 232, 233, 237, 238, 239, 240, 242, 248, 249, 259, 260, 262, 265, 283, 284, 285, 291, 292, 300, 471, 477, 498, 500, 502, 503, 505, 506, 507, 509, 510, 515, 517, 518, 521, 524, 534, 538, 539, and 546 and an antisense strand gene. Specifically, siRNA comprising a sense strand having SEQ ID NO: 5, 6, 15, 18, 40, 48, 49, 59, 62, 69, 77, or 86 and an antisense strand complementary to the sense strand, may reduce 524, 534, 538, 539, or 546 and an antisense strand the expression of mRNA of the SRD5A1-encoding gene, siRNA comprising a sense strand having SEQ ID NO: 205, 208, 228, 231, 232, 233, 237, 238, 239, 240, 242, 248, 249, 259, 260, 262, 265, 283, 284, 285, 291, 292, or 300 and an antisense strand complementary to the sense strand, may reduce the expression of mRNA of the SRD5A2-encoding gene, and siRNA comprising a sense strand having SEQ ID NO: 471, 477, 498, 500, 502, 503, 505, 506, 507, 509, 510, 515, 517, 518, 521, complementary to the sense strand, may reduce the expression of mRNA of the AR-encoding gene. Specifically, it was confirmed that siRNA comprising a sense strand having one selected from the group consisting of 135 10 15 20 25 CA 03054001 2019-08-19 SEQ ID NOS: 48, 49, 69, 86, 231, 259, 260, 262, 498, 500, 506, 509, 510, 518, 538, 539, and 546 and an antisense strand complementary to the sense strand also effectively inhibited the expression of the SRD5A1 protein, the SRD5A2 protein, or the AR protein. The 3'-terminus of the sense strand and the 5'-terminus of the antisense strand form a blunt end. For example, the 5'- terminus of the antisense strand may include, for example, an overhang of 1 nt, 2 nt, 3 nt, 4 nt, 5 nt, 6 nt, 7 nt, or 8 nt. In the present invention, the antisense strand is a polynucleotide complementary to the target gene and has a length of 19 nt or more, for example, 20 nt or more, 21 nt or more, 22 nt or more, 23 nt or more, 24 nt or more, 25 nt or more, 26 nt or more, 27 nt or more, 29 nt or more, 30 nt or more, or 31 nt or more. In one embodiment, the antisense strand may have a length between 19 nt and 24 nt, for example, 19 nt, 20 nt, 21 nt, 22 nt, 23 nt, or 24 nt. The antisense strand may have a sequence partially complementary to the sense strand in consideration of the asymmetric structure. The antisense strand may, for example, be selected from 657, and 664. the group consisting of iSEQ ID NOS: 105, 106, 115, 118, 140, 148, 149, 159, 162, 169, 177, 186, 317, 320, 340, 343, 344, 345, 349, 350, 351, 352, 354, 360, 361, 371, 372, 374, 377, 395, 396, 397, 403, 404, 412, 589, 595, 616, 618, 620, 621, 623, 624, 625, 627, 628, 633, 635, 636, 639, 642, 652, 656, 145 10 15 20 25 CA 03054001 2019-08-19 Specifically, it was confirmed that siRNA comprising an antisense strand selected from the group consisting of SEQ ID NOS: 148, 149, 169, 186, 343, 371, 372, 374, 616, 618, 624, 627, 628, 636, 656, 657, and 664 also effectively inhibited the expression of the SRD5A1 protein, the SRD5A2 protein, or the AR protein. In some embodiments, the sense strand or antisense strand of the siRNA may include one or more chemical modifications. General siRNAs are unable to penetrate through the cell membrane due to reasons such as high negative charge, high molecular weight, and the like, and are rapidly degraded and eliminated in the blood, making it difficult to deliver an amount sufficient for RNAi induction to an actual target site. Currently, in the case of in vitro delivery, numerous highefficiency delivery methods using cationic lipids and cationic polymers have been developed, but in vivo delivery of siRNA as efficient as in vitro delivery thereof is difficult, and siRNA delivery efficiency is reduced by interactions between various proteins present in the living body. Therefore, the inventors of the present application developed cell penetrating asiRNA (cp-asiRNA) having self¬ transfer ability that enables effective intracellular delivery without a separate delivery vehicle by introducing a chemical modification into an asymmetric siRNA structure. 155 10 15 20 25 CA 03054001 2019-08-19 The chemical modification in the sense strand or the antisense strand may comprise, for example, at least one selected from the group consisting of: a modification in which an -OH group at the 2 1 carbon position of a sugar structure in a nucleotide is substituted with -CH3 (methyl), -OCH3 (methoxy), -NH2, -F (fluorine), -0-2- methoxyethyl-O-propyl, -0-2-methylthioethyl, -0-3-aminopropyl, or -O-3-dimethylaminopropyl; a modification in which oxygen in a sugar structure in a nucleotide is substituted with sulfur; a modification of a nucleotide bond to a phosphorothioate, boranophosphate or methyl phosphonate; a modification to peptide nucleic acid (PNA), locked nucleic acid (LNA), or unlocked nucleic acid (UNA); and cholesterol or cell-penetrating peptide binding. In one embodiment, the chemical modification in the sense or antisense strand may be substitution of an -OH group at the 2' carbon position of a sugar structure in a nucleotide with -CH3 (methyl), modification of a nucleotide bond into phosphorothioate, or cholesterol binding. This may enhance the in vivo stability of siRNA. When the -OH group at the 2' carbon position of a sugar structure is substituted with -CH3 (methyl) or when the nucleotide bond is modified into a phosphorothioate, resistance to nucleases may be increased, and binding to the 165 10 15 20 25 CA 03054001 2019-08-19 cell membrane via cholesterol binding may facilitate the intracellular delivery of siRNA. In particular, the chemical modification may include at least one modification selected from the group consisting of: a modification in which an -OH group at the 2' carbon position of a sugar structure in the 5’- or 3 ’-terminus nucleotide of the sense strand is substituted with -CH3 (methyl); a modification in which an -OH group at the 2' carbon position of a sugar structure in two or more nucleotides of the sense strand or the antisense strand is substituted with -CH3 (methyl); a modification of 25% or more of nucleotides bonds in the sense or antisense strand to phosphorothioate; and cholesterol binding at the 3'-terminus of the sense strand. With regard to the modification in which an -OH group at the 2' carbon position of a sugar structure in a nucleotide is substituted with -CH3 (methyl), the -OH group at the 2' carbon position of the sugar structure in a nucleotide positioned at the 5'-terminus of the sense strand may be substituted with - CH3 (methyl). In addition, a 2’-O-methylated nucleoside, in which an -OH group at the 2 1 carbon position of a sugar structure is substituted with -CH3 (methyl), may be continuously or discontinuously included in a 5'-terminus to 3 1 -terminus direction of the sense strand. 2'-O-methylated nucleosides and unmodified nucleosides may be alternately included in the sense strand. 2, 3, 4, 5, 6, 7, or 8 consecutive 2'-O-methylated nucleosides and unmodified 175 10 15 20 25 CA 03054001 2019-08-19 nucleosides may be alternately included in the sense strand. For example, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, 2 to 8, or 8 2'-O-methylated nucleosides may be present in the sense strand. 2'-O-methylated nucleosides may be continuously or discontinuously included in a 5'-terminus to 3'-terminus of the antisense strand. 2'-O-methylated nucleosides and unmodified nucleotides may be alternately included in the antisense strand. 2, 3, 4, 5, 6, 7, or 8 consecutive 2'-0- methylated nucleosides and unmodified nucleosides may be alternately included in the antisense strand. For example, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, or 2-7 2'-O-methylated nucleosides may be present in the antisense strand. With regard to the modification of a nucleotide bond to a phosphorothioate, at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% of bonds between ribonucleotides in the sense strand may be modified into phosphorothioate. In some embodiments, all (100%) of the bonds between ribonucleotides in the sense strand may be modified into phosphorothioate. At least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% of the bonds between ribonucleotides in the antisense strand may be modified into phosphorothioate. In some embodiments, a total (100%) of the 185 10 15 20 25 CA 03054001 2019-08-19 bonds between ribonucleotides in the antisense strand may be modified into phosphorothioate. In another aspect, the present invention relates to a composition for the prevention or treatment of hair loss, which comprises the siRNA. The term "treatment" as used herein means reducing the symptoms of hair loss or the severity of hair loss in a subject to which the composition is administered or preventing the same from being aggravated, and in some cases may include the progression of hair growth. The term "prevention" as used herein means preventing or delaying the initiation of hair loss, or reducing the possibility of developing hair loss. The composition may further be prepared including one or more pharmaceutically acceptable carriers, in addition to the siRNA as an active ingredient. The pharmaceutically acceptable carrier has to be compatible with the active ingredient of the present invention, and may be one selected from physiological saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and a mixture of two or more of these components. If necessary, the composition may include other general additives such as an antioxidant, a buffer, a bacteriostatic agent, and the like. In addition, the composition may be formulated into an injectable preparation such as an aqueous solution, a suspension, an emulsion, or the like by further adding a diluent, a dispersing agent, a surfactant, a binder, and a 195 10 15 20 25 CA 03054001 2019-08-19 lubricant. In particular, the composition may be formulated into a lyophilized preparation. The lyophilized preparation may be formulated using a method commonly used in the art to which the present invention pertains, and a stabilizer for lyophilization may also be added. An administration method of the composition may be determined by one of ordinary skill in the art on the basis of general symptoms of patients and the severity of diseases. In addition, the composition may be formulated into various forms such as powders, tablets, capsules, liquids, injections, ointments, syrups, and the like, and may also be provided in a unit dosage or multiple dosage container, for example, sealed ampoules and vials, and the like. The composition may be administered orally or parenterally. The administration route of the composition according to the present invention may be, but is not limited to, for example, oral administration, intravenous administration, intramuscular administration, intraarterial administration, intramedullary administration, intradural administration, intracardiac administration, transdermal administration, subcutaneous administration, intraperitoneal administration, intestinal administration, sublingual administration, or topical administration. The dosage of the composition according to the present invention varies depending on the body weight, age, gender, and health condition of a patient, diet, administration time, 205 10 15 20 25 CA 03054001 2019-08-19 administration method, excretion rate, severity of disease, or the like, and may be easily determined by those of ordinary skill in the art. In addition, for clinical administration, the composition of the present invention may be formulated into a suitable form using known techniques. In another aspect of the present invention, there is provided a method of preventing or treating hair loss, comprising administering the siRNA to a subject. In another aspect, the present invention relates to a use of the siRNA for preventing or treating hair loss. In another aspect, the present invention relates to a use of the siRNA for preparing a drug for the prevention or treatment of hair loss. Configurations included in the prevention or treatment method according to the present invention are the same as those included in the aforementioned embodiments, and thus the foregoing description may be equally applied to the prevention or treatment method. Hereinafter, the present invention will be described in further detail with reference to the following examples. It will be obvious to those of ordinary skill in the art that these examples are provided for illustrative purposes only and are not intended to limit the scope of the present invention. 215 10 15 20 25 CA 03054001 2019-08-19 [Example 1] Screening for 100 Kinds of RNAi-inducing Double-Stranded Nucleic Acid Molecules Targeting SRD5A1 To obtain high-efficiency RNAi-inducing double-stranded nucleic acid molecules targeting SRD5A1, the target sequence of the SRD5A1 gene was selected and then asiRNA was designed. The asiRNA structure is different from that of generally known siRNAs, and thus when the nucleotide sequences of asiRNA are designed using a general siRNA design program, it may be somewhat difficult to design an optimized asiRNA. Therefore, asiRNA was constructed by the following method. An NCBI db search was used to obtain information on the SRD5A1 gene (mRNA Accession Number: NM_001047.3, NM_001324322.1, NM_001324323.1), which is the target gene pertaining to male pattern hair loss (androgenetic hair loss). For subsequent animal experiments, nucleotide sequences were secured in consideration of the nucleotide sequence homology with mice, and then 100 kinds of asiRNA were designed according to a design method such as the exclusion of sequences having a GC content of 30-62% and 4 or more G or C consecutive bases, and then synthesized by OliX Inc. (Korea). The synthesized sense and antisense strand RNA oligonucleotides were annealed at 95 °C for 2 minutes through incubation at 37 °C for 1 hour, and the asiRNA annealed by 10% polyacrylamide gel electrophoresis (PAGE) was confirmed using a UV transilluminator. [Table 1] 22CA 03054001 2019-08-19 100 Kinds of asiRNA nucleotide sequences targeting 3- oxo-5-alpha-steroid 4-dehydrogenase 1 100 kinds Sequence (5'-3') No. Naae S AS 1 asiSRDSAl 1 GCAGAUACUUGAGCCA (SEQIDNO: 1) UGGCUCAAGUAUCUGCUUUGC (SEQIDNO: 101) 2 asiSRDSAl 2 AAGCAGAUACUUGAGC (SEQIDNO: 2) GCUCAAGUADCUGCUUUGCAA (SEQIDNO: 102) 3 asiSRDSAl 3 CAAAGCAGAUACUUGA (SEQIDNO: 3) UCAAGUAUCUGCUUUGCAAAU (SEQIDNO: 103) 4 asiSRDSAl 4 UGCAAAGCAGAUACUU (SEQIDNO: 4) AAGUAUCUGCUUUGCAAAUAG (SEQIDNO: 104) 5 asiSRDSAl 5 GUGCAGUGUAUGCUGA (SEQIDNO: 5) UCAGCAUACACUGCACAAUGG (SEQIDNO: 105) 6 asiSRDSAl 6 UUGUGCAGUGUAUGCU (SEQIDNO: 6) AGCAUACACUGCACAAUGGCU (SEQIDNO: 10S) 7 asiSRDSAl 7 CAUUGUGCAGUGUAUG (SEQIDNO: 7) CAUACACUGCACAAUGGCUCA (SEQIDNO: 107) 8 asiSRDSAl 8 UUUUGGCUUGUGGUUA (SEQIDNO: 8) UAACCACAAGCCAAAACCUAU (SEQIDNO: 108) 9 asiSRDSAl 9 CGGGCAUGUUGAUAAA (SEQIDNO: 9) UUUAUCAACAUGCCCGUUAAC (SEQIDNO: 109) 10 asiSRDSAl 10 AUAUCCUAAGGAAUCU (SEQIDNO: 10) AGAUUCCUUAGGAUAUGAUCU (SEQIDNO: 110) 23CA 03054001 2019-08-19 11 asiSRDSAl 11 AUCUCAGAAAACCAGG (SEQIDNO: 11) CCUGGUUUUCUGAGAUUCCUU (SEQIDNO: 111) 12 asiSRDSAl 12 GAAUCUCAGAAAACCA (SEQIDNO: 12) UGGUUUUCUGAGAUUCCUUAG (SEQIDNO: 112) 13 asiSRDSAl 13 AGGAAUCUCAGAAAAC (SEQIDNO: 13) GUUUVCUGAGAUUCCUUAGGA (SEQIDNO; 113) 14 asiSRDSAl 14 CUGGAUACAAAAUACC (SEQIDNO: 14) GGUAUUUUGUAUCCAGUAUCU (SEQIDNO: 114) 15 asiSRDSAl 15 OACOGGAUACAAAAUA (SEQIDNO: 15) UAUUUUGUAUCCAGUAUCUCC (SEQIDNO: 115) 16 asiSRDSAl 16 GAUACUGGAUACAAAA (SEQIDNO: 16) UUUUGUAUCCAGUAUCUCCUG (SEQIDNO: ng) 17 asiSRDSAl 17 GAGAUACUGGAUACAA (SEQIDNO: 17) UUGUAUCCAGUAUCUCCUGGU (SEQIDNO: 117) 18 asiSRDSAl 18 AGGAGAUACUGGAUAC (SEQIDNO: 18) GUAUCCAGUAUCUCCUGGUUU (SEQIDNO: 118) 13 asiSRDSAl 19 CCAGGAGAUACUGGAU (SEQIDNO: 19) AUCCAGUAUCUCCUGGUUUUC (SEQIDNO: 119) 20 asiSRDSAl 20 AAUACCAAGGGGAGGC (SEQIDNO: 20) GCCUCCCCUUGGUAUUUUGUA (SEQIDNO: 120) 21 asiSRDSAl 21 AAAAUACCAAGGGGAG (SEQIDNO: 21) CUCCCCUUGGUAUUUUGUAUC (SEQIDNO: 121) 22 asiSRDSAl 22 GAGGCUUAUUUGAAUA (SEQIDNO: 22) UAUUCAAAUAAGCCUCCCCUU (SEQIDNO: 122) 23 asiSRDSAl 23 CAGCCAACUAUUUUGG (SEQIDNO: 23) CCAAAAUAGUUGGCUGCAGUU (SEQIDNO: 123) 24 asiSRDSAl 24 UGCAGCCAACUAUUUU (SEQIDNO: 24) AAAAUAGUUGGCUGCAGUUAC (SEQIDNO: 124) 25 asiSRDSAl 25 ACUGCAGCCAACUAUU (SEQIDNO: 25) AAUAGUUGGCUGCAGUUACGU (SEQIDNO: 125) 26 asiSRDSAl 26 UAACUGCAGCCAACUA (SEQIDNO: 26) UAGUUGGCVGCAGUUACGUAU (SEQIDNO: 126) 27 asiSRDSAl 27 CGUAACUGCAGCCAAC (SEQIDNO: 27) GVUGGCUGCAGUUACGUAVUC (SEQIDNO: 127) 28 asiSRDSAl 28 AUGGAGUGGUGUGGCU (SEQIDNO: 28) AGCCACACCACUCCAUGAUUU (SEQIDNO: 128) 29 asiSRDSAl 29 UCAUGGAGUGGUGUGG (SEQIDNO: 29) CCACACCACUCCAUGAUUUCU (SEQIDNO: 129) 30 asiSRDSAl 30 AAUCAUGGAGUGGUGU (SEQIDNO: 30) ACACCACUCCAUGAUUUCUCC (SEQIDNO: 130) 24CA 03054001 2019-08-19 31 asiSRDSAl 31 GAAAUCAUGGAGUGGU (SEQIDNO: 31) ACCACUCCAUGAUUUCUCCAA (SEQIDNO: 131) 32 asiSRDSAl 32 GAGAAAUCAUGGAGUG (SEQIDNO: 32) CACUCCAUGAUUUCUCCAAAA (SEQIDNO: 132) 33 asiSRDSAl 33 CCCUGGCCAGCUGGUC (SEQIDNO: 33) GACCAGCUGGCCAGGGCAUAG (SEQIDNO: 133) 34 asiSRDSAl 34 UAUGCCCUGGCCAGCU (SEQIDNO: 34) AGCUGGCCAGGGCAUAGCCAC (SEQIDNO: 134) 35 asiSRDSAl 35 GCUAUGCCCUGGCCAG (SEQIDNO: 35) CUGGCCAGGGCAUAGCCACAC (SEQIDNO: 135) 36 asiSRDSAl 36 UCAUGAGUGGUACCUC (SEQIDNO: 36) GAGGUACCACUCAUGAUGCUC (SEQIDNO: 136) 37 asiSRDSAl 37 CAUCAUGAGUGGUACC (SEQIDNO: 37) GGUACCACUCAUGAUGCUCUU (SEQIDNO: 137) 38 asiSRDSAl 38 UCCGGAAAUUUGAAGA (SEQIDNO: 38) UCUUCAAAUUUCCGGAGGUAC (SEQIDNO: 138) 39 asiSRDSAl 39 CAGUGUAUGCUGAUGA (SEQIDNO: 39) UCAUCAGCAUACACUGCACAA (SEQIDNO: 139) 40 asiSRDSAl 40 GCAUGUUGAUAAACAU (SEQIDNO: 40) AUGUUUAUCAACAUGCCCGUU (SEQIDNO: 140) 41 asiSRDSAl 41 GUGGCUAUGCCCUGGC (SEQIDNO: 41) GCCAGGGCAUAGCCACACCAC (SEQIDNO: 141) 42 asiSRDSAl 42 GUGUGGCUAUGCCCUG (SEQIDNO: 42) CAGGGCAUAGCCACACCACUC (SEQIDNO: 142) 43 asiSRDSAl 43 UGGUGUGGCUAUGCCC (SEQIDNO: 43) GGGCAUAGCCACACCACUCCA (SEQIDNO: 143) 44 asiSRDSAl 44 AGUGGUGUGGCUAUGC (SEQIDNO: 44) GCAUAGCCACACCACUCCAUG (SEQIDNO: 144) 45 asiSRDSAl 45 UCUUCACGUUUUGUUU (SEQIDNO: 45) AAACAAAACGUGAAGAAAGCA (SEQIDNO: 145) 46 asiSRDSAl 46 GACUUGAGAACCCUUU (SEQIDNO: 46) AAAGGGUUCUCAAGUCAGGCU (SEQIDNO: 146) 47 asiSRDSAl 47 CUGUUGGCGUGUACAA (SEQIDNO: 47) UUGUACACGCCAACAGVGGCA (SEQIDNO: 147) 48 asiSRDSAl 48 UUAUUUGAAUACGUAA (SEQIDNO: 48) UUACGUAUUCAAAUAAGCCUC (SEQIDNO: 148) 49 asiSRDSAl 49 UUCCAAUGGCGCUUCU (SEQIDNO: 49) AGAAGCGCCAUUGGAAAGCUU (SEQIDNO: 149) 50 asiSRDSAl 50 AAAGGCAUCUGGACUU (SEQIDNO: 50) AAGUCCAGAUGCCUUUGCCUC (SEQIDNO: 150) 25CA 03054001 2019-08-19 51 asiSRDSAl 51 AUCAAUGUGCUCUGGU (SEQIDNO: 51) ACCAGAGCACAUUGAVGGCUC (SEQIDNO: 151) 52 asiSRDSAl 52 GAUCACUUUCUGUAAC (SEQIDNO: 52) GUUACAGAAAGUGAUGAUUCU (SEQIDNO: 152) 53 asiSRDSAl 53 AUCUUCCUUCUAAUAG (SEQIDNO: 53) CUAUUAGAAGGAAGAUUAGCU (SEQIDNO: 153) 54 asiSRDSAl 54 GGCAUUGCUUUGCCUU (SEQIDNO: 54) AAGGCAAAGCAAUGCCAGAUG (SEQIDNO: 154) 55 asiSRDSAl 55 UGUACAAOGGCGAUUA (SEQIDNO: 55) UAAUCGCCAUUGUACACGCCA (SEQIDNO: 155) 56 asiSRDSAl 56 CUUCUCUAUGGACVUU (SEQIDNO: 56) AAAGUCCAUAGAGAAGCGCCA (SEQIDNO: 156) 57 asiSRDSAl 57 UUCCAAGGUGAGGCAA (SEQIDNO: 57) UUGCCUCACCUUGGAAGGGCC (SEQIDNO: 157) 58 asiSRDSAl 58 UCCAAGGUGAGGCAAA (SEQIDNO: 58) UUUGCCUCACCUUGGAAGGGC (SEQIDNO: 158) 59 asiSRDSAl 59 GGUUCAUACGGAGUAA (SEQIDNO: 59) UUACUCCGUAUGAACCACCAC (SEQIDNO: 159) 60 asiSRDSAl 60 AUAGUAGAGAUUGUUG (SEQIDNO: 60) CAACAAUCUCUACUAUAUCCA (SEQIDNO: 160) 61 asiSRDSAl 61 UGUUGUCUGUGAAAUU (SEQIDNO: 61) AAUUUCACAGACAACAAUCUC (SEQIDNO: 161) 62 asiSRDSAl 62 UUCAAGCUCUGGGUAA (SEQIDNO: 62) UUACCCAGAGCUUGAAAUUCU (SEQIDNO: 162) 63 asiSRDSAl 63 UACCUAAUAAGUACCU (SEQIDNO: 63) AGGUACUUAUUAGGUAGAUUG (SEQIDNO: 163) 64 asiSRDSAl 64 AUUGUUGUCUGUGAAA (SEQIDNO: 64) UUUCACAGACAACAAUCUCUA (SEQIDNO: 164) 65 asiSRDSAl 65 CAAAAGAGCAUCAUGA (SEQIDNO: 65) UCAUGAUGCUCUUUUGCUCUA (SEQIDNO: 165) 66 asiSRDSAl 66 CUAUGGACUUUGUAAA (SEQIDNO: 66) UUUAGAAAGUCCAUAGAGAAG (SEQIDNO: 166) 67 asiSRDSAl 67 CUGUCUUUGAUGGCAU (SEQIDNO: 67) AUGCCAUCAAAGACAGUUGUA (SEQIDNO: 167) 68 asiSRDSAl 68 UCUACCUAAUAAGUAC (SEQIDNO: 68) GUACUUAUUAGGUAGAUUGCA (SEQIDNO: 168) 69 asiSRDSAl 69 CUAAUCUUCCUUCUAA (SEQIDNO: 69) UUAGAAGGAAGAUUAGCUAUG (SEQIDNO: 169) 70 asiSRDSAl 70 CAUUUUCAGAACAAUA (SEQIDNO: 70) UAOTGUUCUGAAAAUGCCAUC (SEQIDNO: 170) 26CA 03054001 2019-08-19 71 asiSRDSAl 71 GAUCUCUUCAAGGUCA (SEQIDNO: 71) UGACCUUGAAGAGAUCACUGU (SEQIDNO: 171) 72 asiSRDSAl 72 AGAUUGUUGUCUGUGA (SEQIDNO: 72) UCACAGACAACAAUCUCUACU (SEQIDNO: 172) 73 asiSRDSAl 73 AGAGAUUGUUGUCUGU (SEQIDNO: 73) ACAGACAACAAUCUCUACUAU (SEQIDNO: 173) 74 asiSRDSAl 74 AGACGAACUCAGUGUA (SEQIDNO: 74) UACACUGAGUUCGUCUGACGA (SEQIDNO: 174) 75 asiSRDSAl 75 UCCUCCUGGCCAUGUU (SEQIDNO: 75) AACAUGGCCAGGAGGAUGCAG (SEQIDNO: 175) 76 asiSRDSAl 76 CUUAAUUUACCCAUUU (SEQIDNO: 76) AAAUGGGUAAAUUAAGCACCG (SEQIDNO: 176) 77 asiSRDSAl 77 UGAUGCGAGGAGGAAA (SEQIDNO: 77) UUUCCUCCUCGCAUCAGAAAU (SEQIDNO: 177) 78 asiSRDSAl 78 UGUUCUGUACCUGUAA (SEQIDNO: 78) VUACAGGUACAGAACAUAAVC (SEQIDNO: 178) 79 asiSRDSAl 79 CCUGUAACGGCUAUUU (SEQIDNO: 79) AAAUAGCCGUUACAGGUACAG (SEQIDNO: 179) 80 asiSRDSAl 80 CCAUUGUGCAGUGUAU (SEQIDNO: 80) AUACACUGCACAAUGGCUCAA (SEQIDNO: 180) 81 asiSRDSAl 81 AACAUCCAUUCAGAUC (SEQIDNO: 81) GAUCUGAAUGGAUGUUUAUCA (SEQIDNO: 181) 82 asiSRDSAl 82 UAUCCAAAGUUCAGAA (SEQIDNO: 82) UUCUGAACUUUGGAUACUCUU (SEQIDNO: 182) 83 asiSRDSAl 83 ACCUAAAUACGCUGAA (SEQIDNO: 83) UUCAGCGUAUUUAGGUACUUA (SEQIDNO: 183) 84 asiSRDSAl 84 CGCUGAAAUGGAGGUU (SEQIDNO: 84) AACCUCCAUUUCAGCGUAUUU (SEQIDNO: 184) 85 asiSRDSAl 85 AAUGGAGGUUGAAUAU (SEQIDNO: 85) AUAUUCAACCUCCAUUUCAGC (SEQIDNO: 185) 86 asiSRDSAl 86 AUAUCCUACUGUGUAA (SEQIDNO: 86) UUACACAGUAGGAUAUUCAAC (SEQIDNO: 186) 87 asiSRDSAl 87 UAUGAGACUAGACUUU (SEQIDNO: 87) AAAGUCUAGUCUCAUACACAC (SEQIDNO: 187) 88 asiSRDSAl 88 AAUGUCACAAUCCCUU (SEQIDNO: 88) AAGGGAUUGUGACAVUUAUUG (SEQIDNO: 188) 89 asiSRDSAl 89 GGUCAACUGCAGUGUU (SEQIDNO: 89) AACACUGCAGUUGACCUUGAA (SEQIDNO: 189) 90 asiSRDSAl 90 GCCAUUGUGCAGUCAO (SEQIDNO: 90) AUGACUGCACAAUGGCUACCC (SEQIDNO: 190) 27CA 03054001 2019-08-19 91 asiSRDSAl 91 UGUAAGUGGAGAACUU (SEQIDNO: 91) AAGUUCUCCACUUACACACAG (SEQIDNO: 191) 92 asiSRDSAl 92 CUCUGCCUGUGUGAGU (SEQIDNO: 92) ACUCACACAGGCAGAGCAGCU (SEQIDNO: 192) 93 asiSRDSAl 93 ACCGUGAGCCAUCAAU (SEQIDNO: 93) AUUGAUGGCUCACGGUGAGUG (SEQIDNO: 193) 94 asiSRDSAl 94 GGUUUCUCUCUGUCUU (SEQIDNO: 94) AAGACAGAGAGAAACCAUGUC (SEQIDNO: 194) 95 asiSRDSAl 95 UAGUCUAGACCUAGUU (SEQIDNO: 95) AACUAGGUCUAGACUAGAAGA (SEQIDNO: 195) 96 asiSRDSAl 96 UAGUGUAAAGAAUGAU (SEQIDNO: 96) AUCAUUCUUUACACUACAAGG (SEQIDNO: 196) 97 asiSRDSAl 97 CUGUACCUGUUAUCAA (SEQIDNO: 97) UUGAUAACAGGUACAGGCUAU (SEQIDNO: 197) 98 asiSRDSAl 98 GAAUGCUUCAUGACUU (SEQIDNO: 98) AAGUCAUGAAGCAUUCAACAG (SEQIDNO: 198) 99 asiSRDSAl 99 UGCCUUAUCAUCUCAU (SEQIDNO: 99) AUGAGAUGAUAAGGCAAAGCA (SEQIDNO: 199) 100 asiSRDSAl 100 CAUCUCAUCUGGAGUU (SEQIDNO: 100) AACUCCAGAUGAGAUGAUAAG (SEQIDNO: 200) [Example 2] Screening for RNAi-Inducing Double-Stranded Nucleic Acid Molecules Targeting SRD5A1 5 To confirm gene inhibitory efficiency at the mRNA level, 100 selected kinds of asiRNA were transfected into a HuH-7 cell line at a concentration of 0.3 nM, and qRT-PCR was performed to measure the expression level of SRD5A1 mRNA. The HuH-7 cell line was cultured in Dulbecco's Modified 10 Eagle's Medium (DMEM, Gibco) containing 10% fetal bovine serum (FBS, Gibco) and 100 units/ml of penicillin 100 pg/ml of streptomycin. HuH-7 cells were seeded in a 96-well plate at a density of 5 x 103 cells/well, and a reverse transfection experiment was conducted using asiRNA (0.3 nM, OliX Inc.) and 285 10 15 20 25 CA 03054001 2019-08-19 Lipofectamine 2000 (1 pl/ml, Invitrogen Inc.) in Opti-MEM (a total volume of 100 pl) in accordance with Invitrogen's protocol. After 24 hours, RNA purification and cDNA synthesis were performed in accordance with a basic protocol provided by TOYOBO SuperPrep, the expression level of the SRD5A1 gene was examined with a SRD5A1 TaqMan probe (Hs00602694_mH) using a Bio-Rad CFX-4000 machine, and the results are illustrated in FIGS. 1A and IB. From the results of screening the 100 kinds of asiRNA, the 12 top-ranked asiRNAs (in Table 1, No. 5, 6, 15, 18, 40, 48, 49, 59, 62, 77, and 86) were selected, followed by treatment with 0.3 nM, 1 nM, 3 nM, or 10 nM of asiRNA and western blotting to analyze the protein expression inhibitory effects thereof. HuH-7 cells were seeded in a 6-well plate at a density of 2.5 x 105 cells/well, and then a reverse transfection experiment was conducted using asiRNA and Lipofectamine 2000 (1 pl/ml, Invitrogen Inc.) in Opti-MEM (a total volume of 2 ml) in accordance with Invitrogen's protocol. After 48 hours, the cells were lysed using a mammalian protein extraction buffer (GE healthcare), and then proteins were quantified using a Bradford assay. 10 pg of the protein of each sample was electrophoresed using 12% SDS-PAGE at 80 V for 20 minutes and at 120 V for 1 hour, and then transferred onto a PVDE membrane (Bio-Rad) at 300 mA for 1 hour and 20 minutes. After transfer, the membrane was blocked in 5% skim milk for 1 hour and allowed to react with SRD5A1 295 10 15 20 25 CA 03054001 2019-08-19 antibody (ABcam, abll0123) at a ratio of 1:2000 for 12 hours. The next day, the resulting membrane was allowed to react with anti-Goat HRP (Santa Cruz) at a ratio of 1:10000 for 1 hour, and then the expression levels of the SRD5A1 protein were compared with each other using ChemiDoc (Bio-Rad). From the results of FIG. 2, 4 asiRNAs (in Table 1, No. 48, 49, 69, and 86) capable of inhibiting SRD5A1 protein expression were selected. [Example 3] 16 Kinds of cp-asiRNA Targeting SRD5A1 Gene and Having Self Cell-Penetrating Ability SRD5A1 cp-asiRNAs (a total of 16 strands) were designed by applying three modification patterns to 4 kinds (in Table 1, No. 48, 49, 69, and 86) of asiRNA targeting SRD5A1 according to the number and position of 2'OMe (methyl), phosphorothioate bonds (PS), and cholesterol, and then synthesized by OliX Inc. (Korea). cp-asiRNA enhances endocytosis efficiency and stability and thus may penetrate through the cell membrane with high efficiency without the aid of a delivery vehicle to thereby inhibit target gene expression. The synthesized sense and antisense strand RNA oligonucleotides were annealed at 95 °C for 2 minutes through incubation at 37 °C for 1 hour, and cp-asiRNAs annealed by 10% polyacrylamide gel electrophoresis (PAGE) were confirmed by a UV transilluminator. [Table 2] 30CA 03054001 2019-08-19 16 strands of cp-asiRNA nucleotide sequences targeting SRD5A1 No. Name Sequence (5'-->3') 1 SRD5A1cp-asiRNA S 48 mUUmAUmUUmGAmAUmACmGU*mA*A*cholester ol 2 SRD5A1cp*aslRNA AS 48(2,4) UUACGUAUUCAAAUmAmAG*C*C*U*C 3 SRD5A1cp-asiRNA AS 48(4,4) UUACGUAUUCAAAUmAmAmG*mC*C*U*C 4 SRD5A1cp-asiRNA AS 48(7,4) UUACGUAUUCAAAUmAmAmG*mC‘mC‘mU*mC 5 SRD5A1cp-aslRNA S 49 mUUmCCmAAmUGmGCmGCmUU‘mC*U*cholester ol 6 SRD5A1cp-asiRNA AS 49(2,4) AGAAGCGCCAUUGGmAmAA*G*C*U*U 7 SRD5A1cp-aslRNA AS 49(4,4) AGAAGCGCCAUUGGmAmAmA*mG‘C*U‘U 8 SRD5A1cp*asiRNA AS 49(7,4) AGAAGCGCCAUUGGmAmAmA*mG*mC*mU*mU 9 SRD5A1cp-asiRNA S 69 mCUmAAmUCmUUmCCmUUmCU*mA*A*cholester ol 10 SRD5A1cp-asiRNA AS 69(2,4) UUAGAAGGAAGAUUmAmGC*U*A*U*G 11 SRD5A1cp-asiRNA AS 69(4,4) UUAGAAGGAAGAUUmAmGmC‘mU*A*U*G 12 SRD5A1cp-asiRNA AS 69(7,4) UUAGAAGGAAGAUUmAmGmC*mll*mA*mU*mG 13 SRD5A1cp>aslRNA S 86 mAUmAUmCCmUAmCUmGUmGU*mA*A*cholester ol 14 SRD5A1cp*a$IRNA AS 86(2,4) UUACACAGUAGGAUmAmUU*C*A*A*C 15 SRD5A1cp-asiRNA AS 86(4,4) UUACACAGUAGGAUmAmUmU*mC*A*A*C 16 SRDSAIcp-asiRNA AS 86(7,4) UUACACAGUAGGAUmAmUmU*mC*mA*mA*mC m : 2'-O-Methyl / RNA * : phosphorothioated bond 5 [Example 4] Screening for cp-asiRNA Targeting SRD5A1 Gene and Having Self Cell-Penetrating Ability The inhibitory effects of the 12 kinds of cp-asiRNA shown in Table 2 against SRD5A1 expression were examined. A HuH-7 cell line was incubated with 1 pM or 3 pM of 12 kinds of 10 cp-asiRNA in Opti-MEM media for 24 hours, and then the media were replaced with Dulbecco's Modified Eagle's Medium (Gibco) containing 10% fetal bovine serum (Gibco) and 100 units/ml 315 10 15 20 25 CA 03054001 2019-08-19 penicillin 100 pg/ml streptomycin, and 24 hours after media replacement, SRD5A1 expression was examined at the protein level. As illustrated in FIG. 3, as the result of repeatedly conducting two experiments, it was confirmed that SRD5A1 cpasiRNA #49(2,4) and #86(7,4) exhibited gene inhibitory efficiency of 50% or higher. The inhibitory effects of the two selected kinds of cpasiRNA against SRD5A1 expression were examined in a HuH-7 cell line. The HuH-7 cell line was incubated with 0.3 pM, 1 pM, or 3 pM of each of the two kinds of cp-asiRNA in Opti-MEM media for 24 hours, and then SRD5A1 expression was examined at the mRNA level. As the result of repeatedly conducting four experiments, it was confirmed that SRD5A1 cp-asiRNA #49(2,4) and #86(7,4) exhibited gene inhibitory efficiency of 50% or higher at a concentration of 1 pM or higher (see FIG. 4). [Example 5] Screening for 112 Kinds of RNAi-Inducing Double-Stranded Nucleic Acid Molecules Targeting SRD5A2 To obtain high-efficiency RNAi-inducing double-stranded nucleic acid molecules targeting SRD5A2, the target sequence of the SRD5A2 gene was selected and then asiRNA was designed. The asiRNA structure is different from that of generally known siRNAs, and thus when the nucleotide sequences of asiRNA are designed using a general siRNA design program, it may be somewhat difficult to design an optimized asiRNA. Therefore, asiRNA was constructed by the following method. An NCBI db 32CA 03054001 2019-08-19 search was used to obtain information on the SRD5A2 gene (mRNA Accession Number: NM_000348.3) which is thought to target male pattern hair loss (androgenetic hair loss). For subsequent animal experiments, nucleotide sequences with at least 80% 5 homology to that of mice were secured, and then 100 kinds of asiRNA were designed according to a design method such as the exclusion of sequences having a GC content of 30-62% and 4 or more G or C consecutive bases, and then synthesized by OliX Inc. (Korea). The synthesized sense and antisense strand RNA 10 oligonucleotides were annealed at 95 °C for 2 minutes through incubation at 37 °C for 1 hour, and the asiRNA annealed by 10% polyacrylamide gel electrophoresis (PAGE) was confirmed using a UV transilluminator. 15 [Table 3] 112 strands of asiRNA nucleotide sequences targeting 3- oxo-5-alpha-steroid 4-dehydrogenase 2 33CA 03054001 2019-08-19 112 kinds Sequence (S 1 -3') No. Name S AS 1 asiSRD5A2 1 GUUCCUGCAGGAGCUG (SEQIDNO: 201) CAGCUCCUGCAGGAACCAGGC (SEQIDNO: 313) 2 asiSRD5A2 2 UUCCUGCAGGAGCUGC (SEQIDNO: 202) GCAGCUCCUGCAGGAACCAGG (SEQIDNO: 314) 3 asiSRD5A2 3 UCCUGCAGGAGCUGCC (SEQIDNO: 203) GGCAGCUCCUGCAGGAACCAG (SEQIDNO: 315) 4 asiSRD5A2 4 CCUGCAGGAGCUGCCU (SEQIDNO: 204) AGGCAGCUCCtTGCAGGAACCA (SEQIDNO: 316) 5 asxSRD5A2 5 CUGCAGGAGCUGCCUU (SEQIDNO: 205) AAGGCAQCUCCUOCAGOAACC (SEQIDNO: 317) 6 asxSRD5A2 6 UGCAGGAGCUGCCUUC (SEQIDNO: 206) GAAGGCAGCUCCUGCAGGAAC (SEQIDNO: 318) 7 asiSRD5A2 7 GCAGGAGCUGCCUUCC (SEQIDNO: 207) GGAAGGCAGCUCCOGCAGGAA (SEQIDNO: 319) 8 asiSRE5A2 8 CAGGAGCUGCCUUCCU (SEQIDNO: 208) AGGAAGGCAGCUCCUGCAGGA (SEQIDNO: 320) 9 asiSRD5A2 9 AGOAGCUGCCWCCW (SEQIDNO: 209) AAGGAAGGCAGCUCCUGCAGG (SEQIDNO: 321) 10 aslSRD5A2 10 ACUUCCACAGGACAUU (SEQIDNO: 210) AAUGUCCUGUGGAAGUAAUGU (SEQIDNO: 322) 11 aslSRD5A2 11 CUUCCACAGGACAUUU (SEQIDNO: 211) AAAUGUCCUGUGGAAGUAAUG (SEQIDNO: 323) 12 asiSRD5A2 12 AGGUGGCUUGOTKJACG (SEQIDNO: 212) CGUAAACAAGCCACCUUGUGG (SEQIDNO: 324) 34CA 03054001 2019-08-19 13 asiSRD5A2 13 GGUGGCWGUWACGU (SEQIDNO: 213) ACGUAAACAAGCCACCUVGUG (SEQIDNO: 325) 14 asiSRD5A2 14 GUGGCUUGJUUACGUA (SEQIDNO: 214) UACGUAAACAAGCCACCUUGU (SEQIDNO: 326) 15 asiSRD5A2 15 UGGCOUGUUUACGUAO (SEQIDNO: 215) AUACGUAAACAAGCCACCUUG (SEQIDNO: 327) 16 asiSRD5A2 16 GQCUUGUUUACGUAUG (SEQIDNO: 216) CAUACGUAAACAAGCCACCUU (SEQIDNO: 328) 17 asiSRD5A2 17 GCUUGUUUACGUAUGU (SEQIDNO: 217} ACAUACGUAAACAAGCCACCU (SEQIDNO: 329) IB a«iSRD5A2 18 CUACCUCAAGAUGUUU (SEQIDNO: 218) AAACAUCUUGAGGUAGAACCU (SEQIDNO: 330) 19 aslSRD5A2 19 GGUUCCUGCAGGAGCU (SEQIDNO: 219) AGCUCCUGCAGGAACCAGGCG (SEQIDNO: 331) 20 aslSRD5A2 20 UACUUCCACAGGACAU (SEQIDNO: 220) AUGUCCUGUGGAAGUAAUGUA (SEQIDNO: 332) 21 asiSRD5A2 21 AGACAUACGGUUUAGC (SEQIDNO: 221) GCUAAACCGUAUGUCUGUGUA (SEQIDNO: 333) 22 asiSRD5A2 22 CAGACAUACGGUUUAG (SEQIDNO: 222) CUAAACCGUAUGUCUGUGUAC (SEQIDNO: 334) 23 asiSRD5A2 23 ACAGACAUACGGUUUA (SEQIDNO: 223) UAAACCGUAUGUCUGUGUACC (SEQIDNO: 335) 35CA 03054001 2019-08-19 24 asiSRD5A2 24 CACAGACAUACGGUUU (SEQIDNO: 224) AAACCGUAUGUCUGUGUACCA (SEQIDNO: 336) 25 asiSRD5A2 25 GGAUUCCACAAGGUGG (SEQIDNO: 225) CCACCUUGUGGAAUCCUGUAG (SEQIDNO: 337) 26 asiSRD5A2 26 GAUUCCACAAGGUGGC (SEQIDNO: 226) GCCACCUUGUGGAAUCCUGUA (SEQIDNO: 338) 27 asiSRD5A2 27 AUUCCACAAGGUGGCU (SEQIDNO: 227) AGCCACCUUGUGGAAUCCUGU (SEQIDNO: 339) 28 asiSRD5A2 28 UUCCACAAGGUGGCUU (SEQIDNO: 228) AAGCCACCUUGUGGAAUCCUG (SEQIDNO: 340) 29 asiSRD5A2 29 UCCACAAGGUGGCUUG (SEQIDNO: 229) CAAGCCACCUUGUGGAAUCCU (SEQIDNO: 341) 30 asiSRD5A2 30 CCACAAGGUGGCUUGU (SEQIDNO: 230) ACAAGCCACCUUGUGGAAUCC (SEQIDNO: 342) 31 asiSRD5A2 31 CACAAGGOGGCUUGUU (SEQIDNO: 231) AACAAGCCACCUUGUGGAAUC (SEQIDNO: 343) 32 a»iSRD5A2 32 ACAAGGUGGCUUGUUU (SEQIDNO: 232) AAACAAGCCACCUUGUGGAAU (SEQIDNO: 344) 33 asiSRD5A2 33 CAAGGUGGCUUGUUUA (SEQIDNO: 233) UAAACAAGCCACCUUGUGGAA (SEQIDNO: 345) 34 aslSRD5A2 34 AAGGUGGCUUGUUUAC (SEQIDNO: 234) GUAAACAAGCCACCUUGUGGA (SEQIDNO: 346) 35 asiSRD5A2 35 CUGGAGCCAAUUUCCU (SEQIDNO: 235) AGGAAAUUGGCUCCAGAAACA (SEQIDNO: 347) 36CA 03054001 2019-08-19 36 asiSRD5A2 36 DCUGGAGCCAAUUUCC (SEQIDNO: 236) GGAAAUUGGCUCCAGAAACAU (SEQIDNO: 348) 37 asiSRD5A2 37 UUCUGGAGCCAAUUUC (SEQIDNO: 237) GAAAUUGGCUCCAGAAACAUA (SEQIDNO: 349) 36 asiSRD5A2 38 UUUCUGGAGCCAAUUU (SEQIDNO: 238) AAAUUGGCUCCAGAAACAUAC (SEQIDNO: 350) 39 asiSRD5A2 39 GUUUCUGGAGCCAAUU (SEQIDNO: 239) AAUUGGCUCCAGAAACAUACG (SEQIDNO: 351) 40 asiSRD5A2 40 UGUUUCUGGAGCCAAU (SEQIDNO: 240) AUUGGCUCCAGAAACAUACGU (SEQIDNO: 352) 41 asiSRD5A2 41 AUGUUUCUGGAGCCAA (SEQIDNO: 241) UUGGCUCCAGAAACAUACGUA (SEQIDNO: 353) 42 asiSRD5A2 42 UAUGUUUCUGGAGCCA (SEQIDNO: 242) UGGCUCCAGAAACAUACGUAA (SEQIDNO: 354) 43 asiSRD5A2 43 GUAUGUUUCUGGAGCC (SEQIDNO: 243) GGCUCCAGAAACAVACGUAAA (SEQIDNO: 355) 44 asiSRD5A2 44 GCUCCAGAAACAUACG (SEQIDNO: 244) GCUCCAGAAACAUACGUAAAC (SEQIDNO: 356) 45 asiSRD5A2 45 CAUAGGUUCUACCUCA (SEQIDNO: 245) UGAGGUAGAACCUAUGGUGGU (SEQIDNO: 357) 46 asiSRD5A2 46 AUAGGUUCUACCUCAA (SEQIDNO: 246) UUGAGGUAGAACCUAUGGUGG (SEQIDNO: 358) 47 asiSRD5A2 47 UAGGUUCUACCUCAAG (SEQIDNO: 247) CUUGAGGUAGAACCUAUGGUG (SEQIDNO: 359) 48 asiSRD5A2 48 AGGUUCUACCUCAAGA (SEQIDNO: 248) UCUUGAGGUAGAACCUAUGGU (SEQIDNO: 360) 37CA 03054001 2019-08-19 49 asiSRD5A2 49 GGUUCUACCUCAAGAU (SEQIDNO: 249) AUCUUGAGGUAGAACCUAUGG (SEQIDNO: 361) 50 asiSRD5A2 50 GUUCUACCUCAAGAUG (SEQIDNO: 250) CAUCUUGAGGUAGAACCUAUG (SEQIDNO: 362) 51 asiSRD5A2 51 UUCUACCUCAAGAUGU (SEQIDNO: 251) ACAUCUUGAGGUAGAACCUAU (SEQIDNO: 363) 52 asiSRD5A2 52 UCUACCUCAAGAUGUU (SEQIDNO: 252) AACAUCUUGAGGUAGAACCUA (SEQIDNO: 364) 53 asiSRD5A2 53 CAAAUCUCGGAAAGCC (SEQIDNO: 253) GGCUUUCCGAGAUUUGGGGUA (SEQIDNO: 365) 54 asiSRD5A2 54 AAAUCUCGGAAAGCCC (SEQIDNO: 254) GGGCUUUCCGAGAUUUGGGGU (SEQIDNO: 366) 55 asiSRD5A2 55 AAUCUCGGAAAGCCCU (SEQIDNO: 255) AGGGCUUUCCGAGAUUUGGGG (SEQIDNO: 367) 56 asiSRD5A2 56 GCCCUUAUUCCAUUCA (SEQIDNO: 256) UGAAUGGAAUAAGGGCUUUCC (SEQIDNO: 368) 57 asiSRD5A2 57 CCCUUAUUCCAUUCAU (SEQIDNO: 257) AUGAAUGGAAUAAGGGCUUUC (SEQIDNO: 369) 58 asiSRD5A2 58 CCUUAUUCCAUUCAUC (SEQIDNO: 258) GAUGAAUGGAAUAAGGGCUUU (SEQIDNO: 370) 59 asiSRD5A2 59 CUUAUUCCAUUCAUCU (SEQIDNO: 259) AGAUQAAUGGAAUAAGGGCUU (SEQIDNO: 371) 60 asiSRD5A2 60 UUAUUCCAUUCAUCUU (SEQIDNO: 260) AAGAUGAAUGGAAUAAGGGCU (SEQIDNO: 372) 61 asiSRD5A2 61 UAUUCCAUUCAUCUUU (SEQIDNO: 261) AAAGAUGAAUGGAAUAAGGGC (SEQIDNO: 373) 62 asiSRD5A2 62 AUUCCAUUCAUCUUUU (SEQIDNO: 262) AAAAGAUGAAUGGAAUAAGGG (SEQIDNO: 374) 63 asiSRD5A2 63 UUCCATOCAUCUUUUA (SEQIDNO: 263) UAAAAGAVGAAUGGAAUAAGG (SEQIDNO: 375) 64 asiSRD5A2 64 UCCAUUCAUCUUUUAA (SEQIDNO: 264) UUAAAAGAUGAAUGGAAUAAG (SEQIDNO: 376) 65 asiSRD5A2 65 UCUCACUUUGUUUCCU (SEQIDNO: 265) AGGAAACAAAGUGAGAAAAAU (SEQIDNO: 377) 66 asiSRD5A2 66 UTJCUCACUUUGUUUCC (SEQIDNO: 266) GGAAACAAAGUGAGAAAAAUG (SEQIDNO: 378) 67 as±SRD5A2 67 UUUCUCACUUUGUUUC (SEQIDNO: 267) GAAACAAAGUGAGAAAAAUGC (SEQIDNO: 37») 68 as±SRD5A2 68 UUUUCUCACUUUGUUU (SEQIDNO: 268) AAACAAAGUGAGAAAAADGCA (SEQIDNO: 380) 38CA 03054001 2019-08-19 69 asiSRD5A2 69 UUUUUCUCACUUUGUU (SEQIDNO: 269) AACAAAGUGAGAAAAAUGCAA (SEQIDNO: 381) 70 asiSRD5A2 70 AUUUUUCUCACUUUGU (SEQIDNO: 270) ACAAAGUGAGAAAAAUGCAAA (SEQIDNO: 382) 71 asiSRD5A2 71 UGGCAGGCAGCGCCAC (SEQIDNO: 271) GUGGCGCUGCCUGCCAGCACU (SEQIDNO: 383) 72 asiSRD5A2 72 CUGGCAGGCAGCGGCA (SEQIDNO: 272) UGGCGCUGCCUGCCAGCACUG (SEQIDNO: 384) 73 a®iSRD5A2 73 GGCAGGCAGCGCCACU (SEQIDNO: 273) aguggcgcugccugccagcac (SEQIDNO: 385) 74 asiSRD5A2 74 UGCCAGCCCGCGCCGC (SEQIDNO: 274) gcggcgcgggcuggcaggcgg (SEQIDNO: 386) 75 asiSRD5A2 75 UUACUUCCACAGGACA (SEQIDNO: 275) uguccuguggaaguaauguag (SEQIDNO: 387) 76 asiSRD5A2 76 GUGGAAGUAAUGUAGG (SEQIDNO: 276) CCUACAUUACUUCCACAGGAC (SEQIDNO: 388) 77 asiSRD5A2 77 CCCUGAUGGGUGGUAC (SEQIDNO: 277) GUACCACCCAUCAGGGUAUUC (SEQIDNO: 389) 78 a«iSRD5A2 78 CCUGAUGGGUGGUACA (SEQIDNO: 278) UGUACCACCCAUCAGGGUAUU (SEQIDNO: 390) 79 asiSRD5A2 79 CUGAUGGGUGGUACAC (SEQIDNO: 279) GUGUACCACCCAUCAGGGUAU (SEQIDNO: 391) 80 asiSRD5A2 80 UGAUGGGUGGUACACA (SEQIDNO: 280) UGUGUACCACCCAUCAGGGUA (SEQIDNO: 392) 81 asiSRD5A2 81 GAUGGGUGGUACACAG (SEQIDNO: 281) CUGUGUACCACCCAUCAGGGU (SEQIDNO: 393) 82 asiSRD5A2 82 AUGGGUGGUACACAGA (SEQIDNO: 282) UCUGUGUACCACCCAUCAGGG (SEQIDNO: 394) 39CA 03054001 2019-08-19 83 asiSRD5A2 83 UGGGUGGUACACAGAC ( SEQIDNO: 283) GUCUGUGUACCACCCAUCAGG (SEQIDNO: 395) 84 aslSRD5A2 84 GGGUGGUACACAGACA (SEQIDNO: 284) UGUCUGUGUACCACCCAUGAG (SEQIDNO: 396) 85 asiSRD5A2 85 GGUGGUACACAGACAU ( SEQIDNO: 285) AUGUCUGUGOACCACCCAUCA (SEQIDNO: 397) 86 asiSRD5A2 86 GACAUACGGUUUAGCU (SEQIDNO: 286) AGCTAAACCGUAUGUCUGUGU (SEQIDNO: 398) 87 asiSRD5A2 87 CUUGGGUGUCtTOCUUA ( SEQIDNO: 287) UAAGAAQACACCCAAGCUAAA (SEQIDNO: 399) 88 asiSRO5A2 88 GCUUGGGUGUCUUCUU ( SEQIDNO: 288) AAGAAGACACCCAAGCUAAAC (SEQIDNO: 400) 89 aslSRD5A2 89 AGCUUGGGUGUCUUCU (SEQIDNO: 289) AGAAGACACCCAAGCUAAACC (SEQIDNO: 401) 90 asiSRD5A2 90 UAGCUUGGGUGUCUUC (SEQIDNO: 290) GAAGACACCCAAGCUAAACCG (SEQIDNO: 402) 91 asiSRD5A2 91 GCCAGCUCAGGAAGCC (SEQIDNO: 291) GGCUUCCUGAGCUGGCGCAAU (SEQIDNO: 403) 92 aaiSRD5A2 92 CGCCAGCUCAGGAAGC (SEQIDNO: 292) GCUUCCUGAGCUGGCGCAAUA (SEQIDNO: 404) 93 asiSRD5A2 93 GCGCCAGCUCAGGAAG (SEQIDNO: 293) CUUCCUGAGCUGGCGCAAUAU (SEQIDNO: 405) 94 asiSRD5A2 94 UGGAGCCAAUUUCCUC (SEQIDNO: 294) GAGGAAAUUGGCUCCAGAAAC (SEQIDNO: 406) 40CA 03054001 2019-08-19 95 asiSRD5A2 95 CUCACUUUGUUUCCUU (SEQIDNO: 295) AAGGAAACAAAGUGAGAAAAA (SEQIDNO: 407) 96 asiSRD5A2 96 CAUUUUUCUCACUUUG (SEQIDNO: 296) CAAAGUGAGAAAAAUGCAAAU (SEQIDNO: 408) 97 asiSRD5A2 97 CCAUAGGUUCUACCUC (SEQIDNO: 297) GAGGUAGAACCUAUGGUGGUG (SEQIDNO: 409) 98 asiSRD5A2 98 ACCAUAGGUUCUACCU (SEQIDNO: 298) AGGUAGAACCUAUGGUGGUGA (SEQIDNO: 410) 99 asiSRD5A2 99 CACCAUAGGUUCUACC (SEQIDNO: 299) GGUAGAACCUAVGGUGGUGAA (SEQIDNO: 411) 100 asiSRD5A2 100 CCACCAUAGGUUCUAC (SEQIDNO: 300) GUAGAACCUAUGGUGGUGAAA (SEQIDNO: 412) 101 asiSRD5A2 101 ACCACCAUAGGUUCUA (SEQIDNO: 301) UAGAACCUAVGGUGGUGAAAA (SEQIDNO: 413) 102 asiSRD5A2 102 CACCACCAUAGGUUCU (SEQIDNO: 302) AGAACCUAUGGOGGUGAAAAG (SEQIDNO: 414) 103 asiSRD5A2 103 GGACUACCCCAAAUCU (SEQIDNO: 303) AGAUUUGGGGUAGUCCUCAAA (SEQIDNO: 415) 104 asiSRD5A2 104 AGGACUACCCCAAAUC (SEQIDNO: 304) GAUUUGGGGUAGUCCUCAAAC (SEQIDNO: 416) 105 asiSRD5A2 105 GAGGACUACCCCAAAU (SEQIDNO: 305) AUUUGGGGUAGUCCUCAAACA (SEQIDNO: 417) 106 asiSRD5A2 106 UGAGGACUAGCCCAAA (SEQIDNO: 306) UUUGGGGUAGUCCUCAAACAU (SEQIDNO: 418) 107 asiSRD5A2 107 UUGAGGACUACCCCAA (SEQIDNO: 307) UUGGGGUAGUCCUCAAACAUC (SEQIDNO: 419) 108 asiSRD5A2 108 UUUGAGGACUACCCCA (SEQIDNO: 308) UGGGGUAGUCCUCAAACAUCU (SEQIDNO: 420) 109 asiSRD5A2 109 CCAAAUCUCGGAAAGC (SEQIDNO: 309) GCUUUCCGAGAUUUGGGGUAG (SEQIDNO: 421) 110 asiSRD5A2 110 AGCCCUUAUUCCAUUC (SEQIDNO: 310) GAAUGGAAUAAGGGCUUUCCG (SEQIDNO: 422) 111 asiSRD5A2 111 AAGCCCITUAUUCCAUU (SEQIDNO: 311) AAUGGAAUAAGGGCUUUCCGA (SEQIDNO: 423) 112 asiSRD5A2 112 GGCUAUGCCCUGGCCA (SEQIDNO: 312) UGGCCAGGGCAUAGCCGAUCC (SEQIDNO: 424) [Example 6] Screening for RNAi-Inducing Double-Stranded 5 Nucleic Acid Molecules Targeting SRD5A2 415 10 15 20 CA 03054001 2019-08-19 To confirm gene inhibitory efficiency at the mRNA level, 112 selected kinds of asiRNA were transfected into a HuH-7 cell line at a concentration of 0.3 nM, and qRT-PCR was performed to measure the expression level of SRD5A1 mRNA. The HuH-7 cell line was cultured in Dulbecco's Modified Eagle's Medium (DMEM, Gibco) containing 10% fetal bovine serum (FBS, Gibco) and 100 units/ml of penicillin 100 pg/ml of streptomycin. HuH-7 cells were seeded in a 24-well plate at a density of 5 x 104 cells/well, and a reverse transfection experiment was conducted using asiRNA (0.3 nM, OliX Inc.) and Lipofectamine 2000 (1 pl/ml, Invitrogen Inc.) in Opti-MEM (a total volume of 500 pl) in accordance with Invitrogen's protocol. After 24 hours, total RNA was extracted using TRIzol (TaKaPa), and then cDNA was synthesized using a high-capacity cDNA reverse transcription kit (Applied Biosystems), and the expression level of the SRD5A2 gene was examined using power SYBR green PCR master Mix (Applied Biosystems), the following primers, and a StepOne real-time PCR system (see FIGS. 5A and 5B). The nucleotide sequences of the primers used in the experiment are shown in Table 4 below. [Table 4] Primer nucleotide sequences 425 10 15 20 CA 03054001 2019-08-19 Name Sequence (5 1-3 ) size Human GAPDH Foxward GAG TCA ACG GAT (SEQIDNO: 425) TTG GTC GT 186 Reverse GAC AAG CTT CCC (SEQIDNO: 426) GTT CTC AG Human SRD5A2 Forward TGA ACC TGG GTG (SEQIDNO: 427) GCT TAT GA 242 Reverse GAA AGG AAA GIT (SEQIDNO: 428) GCT TGG G From the results of screening 112 asiRNAs, the 23 top¬ ranked asiRNAs (in Table 3, No. 5, 8, 28, 31, 32, 33, 37, 38, 39, 40, 42, 48, 49, 59, 60, 62, 65, 83, 84, 85, 91, 92, and 100) were selected, and western blotting was performed at a concentration of 10 nM. HuH-7 cells were seeded in a 6-well plate at a density of 2.5 x 105 cells/well, and then a reverse transfection experiment was conducted using asiRNA and Lipofectamine 2000 (1 pl/ml, Invitrogen Inc.) in Opti-MEM (a total volume of 2 ml) in accordance with Invitrogen's protocol. After 48 hours, the cells were lysed using a mammalian protein extraction buffer (GE healthcare), and then proteins were quantified using a Bradford assay. 10 pg of the protein of each sample was electrophoresed using 12% SDS-PAGE at 80 V for 20 minutes and at 120 V for 1 hour, and then transferred onto a PVDE membrane (Bio-Rad) at 300 mA for 1 hour and 20 minutes. After transfer, the membrane was blocked in 5% skim milk for 1 hour and then allowed to react with SRD5A2 antibody (ABcam, abl24877) at a ratio of 1:2000 for 12 hours. The next day, the resulting membrane was allowed to 435 10 15 20 25 CA 03054001 2019-08-19 react with anti-Rabbit HRP (Santa Cruz) at a ratio of 1:10000 for 1 hour, and then the expression levels of the SRD5A2 protein were compared with each other using ChemiDoc (Bio¬ Rad). In the present experiment, 4 asiRNAs (in Table 3, No. 31, 59, 60, and 62) capable of inhibiting SRD5A2 protein expression by about 50% or higher were selected (see FIGS. 6A and 6B). [Example 7] 16 Kinds of cp-asiRNA Targeting SRD5A2 Gene and Having Self Cell-Penetrating Ability SRD5A2 cp-asiRNAs (total 16 strands) were designed by applying three modification patterns to 4 kinds (in Table 3, No. 31, 59, 60, and 62) of asiRNA targeting SRD5A2 according to the number and position of 2'OMe (methyl), phosphorothioate bonds (PS), and cholesterol, and then synthesized by OliX Inc. (Korea). cp-asiRNA enhances endocytosis efficiency and stability and thus may penetrate through the cell membrane with high efficiency without the aid of a delivery vehicle to thereby inhibit the expression of the target gene. The synthesized sense and antisense strand RNA oligonucleotides were annealed at 95 °C for 2 minutes through incubation at 37 °C for 1 hour, and cp-asiRNAs annealed by 10% polyacrylamide gel electrophoresis (PAGE) were confirmed using a UV transilluminator. [Table 5] 44CA 03054001 2019-08-19 16 strands of cp-asiRNA nucleotide sequences targeting SRD5A2 No. Nana Saquanca(5 1 —>3’) 1 SRD5A2cp-asiRNA S 31 mCAnCAmAanGUmGGmCUmU*G*mU*Ucholesterol 2 SRD5A2cp-asiRNA AS 31(2,4) AACAAGCCACCUUGmUmGG*A*A*U*C 3 SRD5A2cp-asiRNA AS 31(4,4) AACAAGCCACCUUGtoUmGmG*nA*A*U*C 4 SRD5A2cp-a«iRNA AS 31(7,4) AACAAGCCACCUUGmUmGmG*mA*mA*mU*mC 5 SRD5A2cp-asiRNA S 59 mCUmUAmTOmCCmAUmUCmA*U*mC*Ucholasterol 6 SRD5A2ap-asiRKA AS 59(2,4) AGAUGAAUGGAAOAmAmGG*G*C*U*U 7 SRD5A2cp-asiRNA AS 59(4,4) AGAUGAAUGGAAUAmAmGmG*mG*C*U*U a SRD5A2ep-asiRNA AS 59(7,4) AGAUGAAUGGAAUAmAmGmG*»G*mC*mU*mU 9 SRD5A2cp-asiRNA S 60 mUUmAUmUCznCAinUUmCAmU*C*lnU*Ucholasterol 10 SRD5A2cp-**iRNA AS 60(2,4) AAGAUGAAUGGAAUmAmAG*G*G*C*U 11 SRD5A2cp-asxRNA AS 60(4,4) AAGAUGAAUGGAAUaAmAmG*iiiG*G*C*U 12 SRD5A2cp-asxRNA AS 60(7,4) AAGAUGAAUGGAAUmAmAmG*ffiG*aG*aC*nU 13 SRD5A2cp-asiRNA S 62 aAUnUCmCAmUUmCAmUC*mV*U*mU*Ucholestaro 1 14 SRD5A2cp-asiRNA AS 62(2,4) AAAAGAUGAAUGGAmAmUA*A*G*G*G 15 SRD5A2cp-aaxRNA AS 62(4,4) AAAAGAUGAAUGGAmAmUmA*mA*G*G*G 16 SRD5A2cp-asiRNA AS 62(7,4) AAAAGAUGAAUGGAmAmUmA*mA*mG*mG*n>G m : 2'-0-Methyl / SNA * : phosphorothioated bond 5 [Example 8] Screening for cp-asiRNA Targeting SRD5A2 Gene and Having Self Cell-Penetrating Ability The inhibitory effects of the 12 kinds of cp-asiRNA shown in Table 5 against SRD5A2 expression were examined. A HuH-7 cell line was incubated with 1 pM or 3 pM of 12 kinds of 10 cp-asiRNA in Opti-MEM media for 24 hours, and then the media were replaced with Dulbecco's Modified Eagle's Medium (Gibco) containing 10% fetal bovine serum (Gibco) and 100 units/ml 455 10 15 20 25 CA 03054001 2019-08-19 penicillin 100 pg/ml streptomycin, and 24 hours after media replacement, SRD5A2 expression was examined at the protein level. As the result of repeatedly conducting two experiments, it was confirmed that SRD5A2 cp-asiRNA #59(4,4) and #62(4,4) exhibited gene inhibitory efficiency of 50% or higher (see FIG. 7). [Example 9] Confirmation of Inhibitory Efficiency of 2 Selected Kinds of cp-asiRNA against Target Gene SRD5A2 Expression The inhibitory effects of the two above-selected kinds of cp-asiRNA against SRD5A2 expression were examined in a HuH- 7 cell line. The HuH-7 cell line was incubated in Opti-MEM media with 1.95 nM, 3.9 nM, 7.8 nM, 15.6 nM, 31.3 nM, 62.5 nM, 125 nM, 250 nM, 500 nM, or 1,000 nM of each of the two kinds of cp-asiRNA for 24 hours, and then SRD5A2 expression was examined at the mRNA level. As the result of repeatedly conducting three experiments, it was confirmed that SRD5A2 cpasiRNA #59(4,4) and #62(4,4) had IC5o values of 22.37 nM and 27.18 nM, respectively (see FIG. 8). The inhibitory effects of the two above-selected kinds of cp-asiRNA against SRD5A2 expression were examined in a HuH- 7 cell line. The HuH-7 cell line was incubated with 0.1 pM, 0.3 pM, 1 pM, or 3 pM of the two kinds of cp-asiRNA in OptiMEM media for 24 hours, and then the media were replaced with Dulbecco's Modified Eagle's Medium (Gibco) containing 10% fetal bovine serum (Gibco) and 100 units/ml penicillin 100 465 10 15 20 25 CA 03054001 2019-08-19 pg/ml streptomycin, and 24 hours after media replacement, SRD5A2 expression was examined at the protein level. As the result of repeatedly conducting two experiments, it was confirmed that, as the treatment concentrations of cpasiSRD5A2 #59(4,4) and #62(4,4) increased, the protein expression of the target gene SRD5A2 was reduced (see FIG. 9). [Example 10] Screening for 118 Kinds of RNAi-Inducing Double-Stranded Nucleic Acid Molecules Targeting AR To obtain high-efficiency RNAi-inducing double-stranded nucleic acid molecules targeting AR, the target sequence of the AR gene was selected and then asiRNA was designed. The asiRNA structure is different from that of generally known siRNAs, and thus when the nucleotide sequences of asiRNA are designed using a general siRNA design program, it may be somewhat difficult to design an optimized asiRNA. Therefore, asiRNA was constructed by the following method. An NCBI db search was used to obtain information on the AR gene (mRNA Accession Number: NM_001011645.2), which is the target gene pertaining to male pattern hair loss (androgenetic hair loss). For subsequent animal experiments, nucleotide sequences with at least 80% homology to that of mice were secured, and then 100 asiRNAs were designed according to a design method such as the exclusion of sequences having a GC content of 30-62% and 4 or more G or C consecutive bases, and then synthesized by OliX Inc. (Korea). The synthesized sense and antisense strand RNA oligonucleotides were annealed at 95 °C for 2 minutes through 47CA 03054001 2019-08-19 incubation at 37 °C for 1 hour, and the asiRNA annealed by 10% polyacrylamide gel electrophoresis (PAGE) was confirmed using a UV transilluminator. 5 [Table 6] 118 strands of asiRNA nucleotide sequences targeting androgen receptor No. Sequence (5'-3') Name S (16mer) As (21mer) 1 asiARl GAGAUGAAGCUUCUGG (SEQIDNO: 429) CCAGAAGCUUCAUCUCCACAG (SEQIDNO: 547) 2 asiAR2 GGAGAUGAAGCUUCUG (SEQIDNO: 430) CAGAAGCUUCAUCUCCACAGA (SEQIDNO: 54B) 3 asiAR3 GUGGAGAUGAAGCUUC (SEQIDNO: 431) GAAGCUUCAUCUCCACAGAUC (SEQIDNO: 549) 4 asiAR4 UGUGGAGAUGAAGCUU (SEQIDNO: 432) AAGCUUCAUCUCCACAGAUCA (SEQIDNO: 550) 5 asiAR5 UCUGUGGAGAUGAAGC (SEQIDNO: 433) GCUUCAUCUCCACAGAUCAGG (SEQIDNO: 551) 6 asiAR6 UGAUCUGUGGAGAUGA (SEQIDNO: 434) UCAUCUCCACAGAUCAGGCAG (SEQIDNO: 552) 7 asiAR7 CUGAUCUGUGGAGAUG (SEQIDNO: 435) CAUCUCCACAGAUCAGGCAGG (SEQIDNO: 553) 8 asiARS AAGACCUGCCUGAUCU (SEQIDNO: 436) AGAUCAGGCAGGUCUUCUGGG (SEQIDNO: 554) 9 asiAR9 UUUCCACCCCAGAAGA (SEQIDNO: 437) UCUUCUGGGGUGGAAAGUAAU (SEQIDNO: 555) 10 asiARlO ACUUUCCACCCCAGAA (SEQIDNO: 438) UUCUGGGGUGGAAAGUAAUAG (SEQIDNO: 556) 48CA 03054001 2019-08-19 11 asiARll AAGGGAAACAGAAGUA (SEQIDNO: 439) UACUUCUGUUUCCCUUCAGCG (SEQIDNO: 557) 12 asiAR12 GAAGGGAAACAGAAGU (SEQIDNO: 440) ACUUCUGUUUCCCUUCAGCGG (SEQIDNO: 558) 13 asiARI3 CUGAAGGGAAACAGAA (SEQIDNO: 441) UUCUGUUUCCCUUCAGCGGCU (SEQIDNO: 559) 14 asiAR14 GAAAAGAGCCGCUGAA (SEQIDNO: 442) UUCAGCGGCUCUUUUGAAGAA (SEQIDNO: 560) 15 asiAR15 UCAAAAGAGCCGCUGA (SEQIDNO: 443) UCAGCGGCUCUUUUGAAGAAG (SEQIDNO: 561) 16 asiARlS CUUCAAAAGAGCCGCU (SEQIDNO: 444) AGCGGCUCUUUUGAAGAAGAC (SEQIDNO: 562) 17 asiARl? CUUCUUCAAAAGAGCC (SEQIDNO: 445) GGCUCUUUUGAAQAAGACCUU (SEQIDNO: 563) 18 asiARlS UCUUCUUCAAAAGAGC (SEQIDNO: 446) GCUCUUUUGAAGAAGACCUUG (SEQIDNO: 564) 19 aaiAR19 AGKTOCUUCUUCAAAAG (SEQIDNO: 447) CXKJUUGJULGAAflJUXUUG (SEQIDNO: 565) 20 a«lM20 AAGCAGGGAUGACUCU (SEQIDNO: 448) AGAGVGAOCCCUGCUUCAUAA (SEQIDNO: 566) 21 aslAR21 UGAAGCAGGGAUGACU (SEQIDNO: 449) AGUCAUCCCTGCUUCAUAACA (SEQIDNO: 567) 22 aaiAR22 UUAVGAAGCAGGGAUG (SEQIDNO: 450) CAOCCCUGCUVCAUAACAUUU (SEQIDNO: 568) 23 asiAR23 UGUUAUGAAGCAGGGA (SEQIDNO: 451) UCCCUGCiroCAUAACAUUUCC (SEQIDNO: 569) 24 aaiAR24 AUGUUAUGAAGCAGGG (SEQIDNO: 452) CCCUGCUUCAUAACAUUUCCG (SEQIDNO: 570) 25 asiAR2S GCUAUGAAUGUCAGCC (SEQIDNO: 453) GGCUGACAUUCAUAGCCUUCA (SEQIDNO: 571) 26 asiAR26 GGCUAUGAAUGUCAGC (SEQIDNO: 454) GCtXMClUnK^JUXCWCAA (SEQIDNO: 572) 27 a»iAR27 GAAGGCUAUGAAUGUC (SEQIDNO: 455) GACAUUCAUAGCCUUCAAQOT (SEQIDNO: 573) 28 aaiAR28 UOGAAGGCUAVGMLUG (SEQIDNO: 456) CAUUCAUAGCCUUCAAUGOGU (SEQIDNO: 574) 29 asiAR29 GAAGCCAUUGAGCCAG (SEQIDNO: 457) CQGGCUCAAUGGCUUCCAGGA (SEQIDNO: 575) 30 asiAR30 CUGGCUUCCGCAACUU (SEQIDNO: 458) AAGUVGCGGAAGCCAGGCAAG (SEQIDNO: 576) 49CA 03054001 2019-08-19 31 asiAR31 UGCCUGGCUUCCGCAA (SEQIDNO: 459) UUGCGGAAGCCAGGCAAGGCC (SEQIDNO: 577) 32 asiAR32 AGUGGGCCAAGGCCtJU (SEQIDNO: 460) AAGGCCOUGGCCCACUUGAiCC (SEQIDNO: 578) 33 asiAR33 CObGGAUGCOCUACUU (SEQIDNO: 461) AAOUUSAaCAOCCUGGAGWG (SEQIDNO: 579) 34 a«iAR34 UCCAGGAUGCOOUACU (SEQIDNO: 462) AGUAGAGCAUCCUGGAGOUGA (SEQIDNO: 580) 35 asiAR35 AACUCCAGGAOGCUCU (SEQIDNO: 463) JM3AGCAGCC0GGAGQUGACAU (SEQIDNO: 581) 36 a«lAR36 UACCGCAGGCACAAGU (SEQIDNO: 464) ACQVGOGOADGCGGUACUCAU (SEQIDNO: 582) 37 a«iAR37 AGOACCGCAXJGCACAA (SEQIDNO: 465) UUGUGCAOGCGGVACUCAUUG (SEQIDNO: 583) 38 *s£AR38 CAAUGAGUACCGCAUG (SEQIDNO: 466) CAUGCGGUACUCAUXX3AAAAC (SEQIDNO: 584) 39 asiAR39 UCAAUGAGUACCGCAU (SEQIDNO: 457} AUGCGGUACUCAUUGAAAACC (SEQIDNO: 585) 40 asiAR40 UUGAAUGAGUACCGCA (SEQIDNO: 468) ugcgguactcaotgaaaacca (SEQIDNO: 586) 41 a«£AR41 UUGGAUGGCUCCAAAU (SEQIDNO: 469) AUUUGGAGCCAUCCAAACUCU (SEQIDNO: 587) 42 asiAR42 AGUUUGGAVGGCUCCA (SEQIDNO: 470) UGGAGCCAUCCAAACUCTOGA (SEQIDNO: 588) 43 asiAR43 AGAGUUUGGAUGGCUC (SEQIDNO: 471) GAGCCAUCCAAACUCTUGAGA (SEQIDNO: 589) 44 a«iAR44 UCAAGGAACUCGAUCG (SEQIDNO: 472) CGAUCGAGUUCCUUGAUGUAG (SEQIDNO: 590) 45 asxAR45 CAUCAAGGAACUCGAU (SEQIDNO: 473) AUCGAGUUCCUUGAUGUAGUU (SEQIDNO: 591) 46 asiAR46 CUACAUCAAGGAACUC (SEQIDNO: 474) GAGUUCCUUGAUGUAGUUCAU (SEQIDNO: 592) 47 asiAR47 GAACUACAUCAAGGAA (SEQIDNO: 475) UUCCUUGAUGUAGGUCAUUCG (SEQIDNO: 593) 48 asiAR48 CUUCGAAOGAACUACA (SEQIDNO: 476) UGUAGUUCAUUCGAAGUTJCAU (SEQIDNO: 594) 49 as±AR49 UGAACUUCGAAUGAAC (SEQIDNO: 477) GXJUCAUUCGAAGUUCAUCAAA (SEQIDNO: 595) 50 asiARSO UGAUGAACUUCGAAUG (SEQIDNO: 478) CAUUCGAAGUUCAUCAAAGAA (SEQIDNO: 596) 51 aaiAR51 GGGCUGAAAAAUCAAA (SEQIDNO: 479) UUUGAOTUUUCAGCCCAnCCA (SEQIDNO: 597) 50CA 03054001 2019-08-19 52 asiAR52 GAUGGGCUGAAAAAUC (SEQIDNO: 480) GAUUTTUUCAGCCCAUCCACUG (SEQIDNO: 598) 53 asiAR53 VAUUCCAGUGGAUGGG (SEQIDNO: 481) CCCAUCCACUGGAAUAAUGCU (SEQIDNO: 599) 54 asiAR54 CAUUAUUCCAGUGGAU (SEQIDNO: 482) AUCCACUGGAAUAAUGCUGAA (SEQIDNO: 600) 55 asiAR55 AG<AVUAUUCCAOTGG (SEQIDNO: 483) CCACUGGAAUAAUGCUGAAGA (SEQIDNO: 601) 56 &C1AR56 UUCAGCAUUAUUCGAG (SEQIDNO: 484) CUGGAAUAAUGCUGAAGAGAG (SEQIDNO: 602) 57 asiAR57 CUCUUCAGCAUUAUUC (SEQIDNO: 485) GAAUAADGCUGAAGAGAGCAG (SEQIDNO: 603) 58 asiARSS CUGCUCUCUUCAGCAU (SEQIDNO: 486) AUGCUGAAGAGAGCAGUGCUU (SEQIDNO: 604) 50 asiARSd AAGCACUGCUCUCUUC (SEQIDNO: 487) GAAGAGAGCAGUGCUUUCAUG (SEQIDNO: 605) 60 *siAR60 GAAAGCACUGCUCUCU (SEQIDNO: 488) AGAGAGCAGUGCUUUCAUGCA (SEQIDNO: 606) 61 asiAR61 CAUGAAAGGACUGCUC (SEQIDNO: 489) GAGCAGUGCUUUCAUGCACAG (SEQIDNO: 607) 62 asiAR62 GUGCAUGAAAGCACUG (SEQIDNO: 490) CAGUGCUUUCAUGCACAGGAA (SEQIDNO: 608) 63 asiAR63 UUCCUGUGCAUGAAAG (SEQIDNO: 491) CUUUCAUGCACAGGAAUUCCU (SEQIDNO: 609) 64 asiAR64 GAAUUCCUGUGCAUGA (SEQIDNO: 492) UCAUGCACAGGAAUUCCUGGG (SEQIDNO: 610) 65 asiAR65 AGGAAUUCCUGUGCAU (SEQIDNO: 4 93) AUGCACAGGAAUUCCUGGGGG (SEQIDNO: 611) 66 asiAR66 UCACCAAGCUCCUGGA (SEQIDNO: 494) UCCAGGAGCUUGGUGAGCUGG (SEQIDNO: 612) 67 asiAR67 ACCAGCUCACCAAGCU (SEQIDNO: 495) AGCUUGGUGAGCUGGUAGAAG (SEQIDNO: 613) 68 asiAR68 CUACCAGCUCACCAAG (SEQIDNO: 496) CUUGGUGAGCUGGUAGAAGCG (SEQIDNO: 614) 69 asiAR69 ACCUGCUAAUCAAGUC (SEQIDNO: 497) GACUUGAUUAGCAGGUCAAAA (SEQIDNO: 615) 70 asiAR70 GACCUGCUAAUCAAGU (SEQIDNO: 498) ACUUGAUUAGCAGGUCAAAAG (SEQIDNO: 616) 51CA 03054001 2019-08-19 71 asiAR71 UUUGACCUGCUAAUCA (SEQIDNO: 499) UGAUUAGCAGGUCAAAAGUGA (SEQIDNO: 617) 72 asiAR72 CUUUUGACCUGCUAAU (SEQIDNO: 500) AUUAGCAGGUCAAAAGUGAAC (SEQIDNO: 618) 73 aaiAR73 UCACUUUUGACCUGCU (SEQIDNO: 501) AGCAGGUCAAAAGUGAACUGA (SEQIDNO: 619) 74 aaiAR74 UUCACUUUUGACCUGC (SEQIDNO: 502) GCAGGUCAAAAGOGAACUGAU (SEQIDNO: 620) 75 aaiAR75 CAGUUCACUUUUGACC (SEQIDNO: 503) GGUCAAAAGUGAACUGAUGCA (SEQIDNO: 621) 76 aalAR76 CAUCAGUUCACUUUUG (SEQIDNO: 504) CAAAAGUGAACUGAUGCAGCU (SEQIDNO: 622) 77 aslAR77 CUGCAUCAGUUCACUU (SEQIDNO: 505) AAGUGAACUGAUGCAGCUCUC (SEQIDNO: 623) 78 asiAR78 GCUGCAUCAGUUCACU (SEQIDNO: 506) AGUGAACUGAUGCAGCUCUCU (SEQIDNO: 624) 79 aalAR79 CCAUCTAUWCCACAC (SEQIDNO: 507) GUGOGGAAAUAGAUGGGCUUG (SEQIDNO: 625) 80 asiAR80 CCCAUCUAUUUCCACA (SEQIDNO: 508) UGUGGAAAUAGAUGGGCUUGA (SEQIDNO: 626) 81 aslARSl AGCCCAUCUAUUUCCA (SEQIDNO: 509) UGQAAAUAGAUGGGCUUGACU (SEQIDNO: 627) 82 asiAR82 UCAAGCCCAUCUAUUU (SEQIDNO: 510) AAAUAGAUGGGCUUGACUUUC (SEQIDNO: 628) 83 asiAR83 GGAAAGUCAAGCCCAU (SEQIDNO: 511) AUGGGCUUGACUUUCCCAGAA (SEQIDNO: 629) 84 asiAR84 CUGGGAAAGUCAAGCC (SEQIDNO: 512) GGCUUGACUUUCCCAGAAAGG (SEQIDNO: 630) 85 asiAR85 UUUCUGGGAAAGUCAA (SEQIDNO: 513) UUGACUUUCCCAGAAAGGAUC (SEQIDNO: 631) 86 asiAR86 UCCUUUCUGGGAAAGU (SEQIDNO: 514) ACUUUCCCAGAAAGGAUCUUG (SEQIDNO: 632) 87 asiAR87 CCAAGAUCCUUUCUGG (SEQIDNO: 515) CCAGAAAGGAUCVUGGGCACU (SEQIDNO: 633) 88 asiAR88 UGCCCAAGAUCCUUUC (SEQIDNO: 516) GAAAGGAUCUUGGGCACTUGC (SEQIDNO: 634) 89 asiAR89 AAGUGCCCAAGAUCCU (SEQIDNO: 517) AGGAUCUUGGGCACUUGCACA (SEQIDNO: 635) 90 asiAR90 UGCAAGUGCCCAAGAU (SEQIDNO: 518) AUCUUGGGCACUUGCACAGAG (SEQIDNO: 636) 52CA 03054001 2019-08-19 91 aaiAR91 UCUCUGUGCAAGUGCC (SEQIDNO: 519) GGCACUUGCACAGAGAUGAUC (SEQIDNO: 637) 92 asiAR92 UCAUCUCUGUGCAAGU (SEQIDNO: 520) ACUUGCACAGAGAOGAUCUCU (SEQIDNO: 638) 93 asiAR93 AGAUCAUCUCUGUGCA (SEQIDNO: 521) UGCACAGAGAUGAOCUCUGCC (SEQIDNO: 639) 94 aaiAR94 CAGAGAUCAUCUCUGU (SEQIDNO: 522) ACAGAGAUGAUCUCUGCCAUC (SEQIDNO: 640) 95 asiAR95 CACUGGCACUAAAAAA (SEQIDNO: 523) OTUUUUAGUGCOAOTGAACAU (SEQIDNO: 641) 96 asiAR96 UCACUGGCACUAAAAA (SEQIDNO: 524) UUUUUAGUGCCAGUGAACAUA (SEQIDNO: 642) 97 asiAR97 GUUCACUGGCACUAAA (SEQIDNO: 525) UUUAGUGCCAGUGAACAUACA (SEQIDNO: 643) 98 asiAR98 UAUGUUCACUGGCACO (SEQIDNO: 526) AGUGCCAGUGAACAUACAUAA (SEQIDNO: 644) 99 asiAR99 UGUAUGXJUOACUGGCA (SEQIDNO: 527) UGCCAGUGAACAUAOAUAAAA (SEQIDNO: 645) 100 asiARlOO UAUGUAUGOUCACUGG (SEQIDNO: 528) CCAGUGAACAUACAVAAAAAU (SEQIDNO: 646) 101 asiARlOl GGGUAGUUGCUGAGGU (SEQIDNO: 529) ACCUCAGCAACUACCCAAAGG (SEQIDNO: 647) 53CA 03054001 2019-08-19 102 aaiAR102 UGGGUAGUUGCUGAGG (SEQIDNO: 530) CCUCAGCAACUACCCAAAGGA (SEQIDNO: 648) 103 aaiAR103 CUUUGGGUAGUUGCUG (SEQIDNO: 531) CAGCAACUACCCAAAGGACAG (SEQIDNO: 649) 104 aaiAR104 CCUUUGGGUAGUUGCU (SEQIDNO: 532) AGCAACUACCCAAAGGACAGA (SEQIDNO: 650) 105 a*iAR105 CCACCAUCCACAUGAU (SEQIDNO: 533) AUCAUGUGGAUGGUGGACAUA (SEQIDNO: 651) 106 aaiAR106 CAUUAGUGCCUCUUUG (SEQIDNO: 534) CAAAGAGGCACUAAUGCUUGC (SEQIDNO: 652) 107 asiAR107 GCAUUAGUGCCUCUUU (SEQIDNO: 535) AAAGAGGCACUAAUGCUUGCU (SEQIDNO: 653) 108 asiAR108 AGCAUUAGUGCCUCUU (SEQIDNO: 536) AAGAGGGACUAAUGCUUGCUC (SEQIDNO: 654) 10» asiAR109 AAGCAUUAGUGCCUCU (SEQIDNO: 537) AGAGGCACTAAUGCUUGCUCC (SEQIDNO: 655) 110 asiARllO GCCCAUGUUAGCUUAU (SEQIDNO: 538) AUAAGCUAACAUGGGCACUAG (SEQIDNO: 656) 111 asiARlll GAAACUUGUUUGUUGG (SEQIDNO: 539) CCAACAAACAAGUUUCUGCCA (SEQIDNO: 657) 112 asiAR112 gcagaaacuugutjugu (SEQIDNO: 540) ACAAACAAGUUUCUGCOAUUU (SEQIDNO: 658) 113 asiAR113 AUGGCAGAAACUUGUU (SEQIDNO: 541) AAOAAGUUUCBGCCAUUUUUA (SEQIDNO: 659) 114 asiAR114 AAUGGCAGAAACUUGU (SEQIDNO: 542) ACAAGUUUCUGCCAUUUUUAA (SEQIDNO: 660) 115 asiARllS GGAAUCUUUUGUUGCU (SEQIDNO: 543) AGCAACAAAAGAUUCCAAGAU (SEQIDNO: 661) 116 asiAR116 UGGAAUCUUUUGUUGC (SEQIDNO: 544) GCAACAAAAGAUUCCAAGAUU (SEQIDNO: 662) 117 asiAR117 UAGUGUUCUGUUCUCO (SEQIDNO: 545) AGAGAACAGAACACUAGCGCU (SEQIDNO: 663) 118 a«iAR118 CUAGUGUUCUGUUCUC (SEQIDNO: 546) GAGAACAGAACACUAGCGCUU (SEQIDNO: 664) [Example 11] Screening for RNAi-Inducing Double-Stranded 5 Nucleic Acid Molecules Targeting AR 545 10 15 20 25 CA 03054001 2019-08-19 To confirm gene inhibitory efficiency at the mRNA level, the 118 selected asiRNAs were transfected into an A549 cell line at a concentration of 0.3 nM, and qRT-PCR was performed to measure the expression level of AR mRNA. The A549 cell line was cultured in Dulbecco's Modified Eagle's Medium (DMEM, Gibco) containing 10% fetal bovine serum (FBS, Gibco) and 100 units/ml of penicillin 100 pg/ml of streptomycin. A549 cells were seeded in a 96-well plate at a density of 5 x 103 cells/well, and a transfection experiment was conducted using asiRNA (0.3 nM, OliX Pharmaceuticals Inc.) and RNAiMAX (1 pl/ml, Invitrogen Inc.) in Opti-MEM (a total volume of 100 pl) in accordance with Invitrogen's protocol. After 24 hours, RNA purification and cDNA synthesis were performed in accordance with a basic protocol provided by TOYOBO SuperPrep, the expression level of the AR gene was examined with an AR TaqMan probe (T) using a Bio-Rad CFX-4000 machine. First, 88 kinds of asiRNA from among the 118 kinds of asiRNA were subjected to an asiRNA screening experiment and the 13 top-ranked asiRNAs (in Table 6, No. 43, 49, 67, 70, 72, 74, 75, 77, 78, 79, 81, 82, and 87) were selected on the basis of inhibitory efficacy against the expression of the target gene, and the 13 selected asiRNAs and the 30 remaining asiRNAs (in Table 6, Nos. 88 to 118) were subjected to a secondary asiRNA screening experiment (see FIGS. 10A and 10B). The 20 top-ranked asiRNAs (in Table 6, No. 43, 49, 70, 72, 74, 75, 77, 78, 79, 81, 82, 87, 89, 90, 93, 96, 106, 110, 555 10 15 20 25 CA 03054001 2019-08-19 111, and 118) having gone through secondary asiRNA screening were selected on the basis of inhibitory efficacy against the expression of the target gene, and an experiment for confirming the inhibitory effect of the 20 selected asiRNAs against AR expression at the protein level was performed. A549 cells were seeded in a 12-well plate at a density of 5 x 104 cells/well, and then a transfection experiment was conducted using asiRNA (0.3 nM, OliX Pharmaceuticals Inc.) and RNAiMAX (1 pl/ml, Invitrogen Inc.) in Opti-MEM (a total volume of 1 ml) in accordance with Invitrogen's protocol. After 48 hours, the cells were lysed using a mammalian protein extraction buffer (GE healthcare), and then proteins were quantified using a Bradford assay. 20 pg of the protein of each sample was electrophoresed using 10% SDS-PAGE at 80 V for 20 minutes and at 120 V for 1 hour, and then transferred onto a PVDE membrane (Bio-Rad) at 300 mA for 1 hour. After transfer, the membrane was blocked in 5% skim milk for 1 hour and allowed to react with AR antibody (ABcam, abl33273) at a ratio of 1:2000 for 12 hours. The next day, the resulting membrane was allowed to react with anti-Rabbit HRP (Santa Cruz) at a ratio of 1:5000 for 1 hour, and then the expression levels of the AR protein were compared with each other using ChemiDoc (Bio¬ Rad). From the results, the 9 top-ranked asiRNAs (No. 70, 72, 78, 81, 82, 90, 110, 111, and 118) capable of more effectively inhibiting AR protein expression were selected (see FIG. 11). 565 10 15 20 CA 03054001 2019-08-19 The 9 top-ranked asiRNA candidates (in Table 6, No. 70, 72, 78, 81, 82, 90, 110, 111, and 118) having gone through asiRNA screening were selected on the basis of inhibitory efficacy against the expression of the target gene, and an experiment for confirming the inhibitory effects of the 9 selected asiRNA candidates against AR expression at the mRNA and protein levels and a lower concentration (0.1 nM) was conducted. A549 cells were seeded in a 12-well plate at a density of 5 x 104 cells/well, and a transfection experiment was conducted using asiRNA and RNAiMAX (1 pl/ml, Invitrogen Inc.) in Opti-MEM (a total volume of 0.5 ml) in accordance with Invitrogen's protocol. After 48 hours, total RNA was extracted using TRIzol (TaKaPa), and then cDNA was synthesized using a high-capacity cDNA reverse transcription kit (Applied Biosystems), and the expression level of the AR gene was examined using power SYBR green PCR master Mix (Applied Biosystems), the primers shown in Table 7 below, and a StepOne real-time PCR system. [Table 7] Primer nucleotide sequences 57CA 03054001 2019-08-19 Nas* Sequence (5’-3•) else Hunan GAPDH Forward GAG IGA ACG GAT TTG GTC GT (SEQIDNO: 665) 186 Reverse GAG AAG CTT CCC GIT CTC AG (SEQIDNO: 666) Human AR Forward GGG GCT AGA CTG CTC AAC TG (SEQIDNO: 667) 191 Reverse GCC AAG TTT TGG CTG AAG AG (SEQIDNO: 668) In addition, A549 cells were seeded in a 12-well plate at a density of 5 x 104 cells/well, and a transfection 5 experiment was conducted using asiRNA and RNAiMAX (1 pl/ml, Invitrogen Inc.) in Opti-MEM (a total volume of 0.5 ml) in accordance with Invitrogen's protocol. After 48 hours, the cells were lysed using a mammalian protein extraction buffer (GE healthcare), and then proteins were quantified using a 10 Bradford assay. 20 pg of the protein of each sample was electrophoresed using 10% SDS-PAGE at 80 V for 20 minutes and at 120 V for 1 hour, and then transferred onto a PVDE membrane (Bio-Rad) at 300 mA for 1 hour. After transfer, the membrane was blocked in 5% skim milk for 1 hour and allowed to react 15 with AR antibody (ABcam, abl33273) at a ratio of 1:2000 for 12 hours. The next day, the resulting membrane was allowed to react with anti-Rabbit HRP (Santa Cruz) at a ratio of 1:5000 for 1 hour, and then the expression levels of the AR protein were compared with each other using ChemiDoc (Bio-Rad). As the 585 10 15 20 CA 03054001 2019-08-19 result of the experiment for the 9 selected asiRNAs, it was confirmed that asiRNA #72, 78, and 110 exhibited gene inhibitory efficiency of 50% or higher efficiently even at a concentration of 0.1 nM (see FIG. 12). [Example 12] 9 Kinds of cp-asiRNA Targeting AR Gene and Having Self Cell-Penetrating Ability AR cp-asiRNAs (a total of 9 kinds) were designed by applying three modification patterns to 3 kinds of asiRNA targeting AR according to the number and position of 2'OMe (methyl), phosphorothioate bonds (PS), and cholesterol, and then synthesized by Dharmacon. cp-asiRNA enhances endocytosis efficiency and stability, and thus may penetrate through the cell membrane with high efficiency without the aid of a delivery vehicle to thereby inhibit the expression of the target gene. The synthesized sense and antisense strand RNA oligonucleotides were annealed at 95 °C for 2 minutes through incubation at 37 °C for 1 hour, and cp-asiRNAs annealed by 10% polyacrylamide gel electrophoresis (PAGE) were confirmed using a UV transilluminator. [Table 8] 9 kinds of cp-asiRNA nucleotide sequences targeting AR 59CA 03054001 2019-08-19 No. Name Sequence (5' -3’) 1 cp-asiAR72 S mCVmUUmUGDACmCUnGCmUAa*A*U*chol 2 cp-asiAR72 AS (7, 4) AUUAGCAGOTCAAAmAmGmU*mG*mA*mA*mC 3 cp-asiAR72 AS (4, 4) AUUAGCAGGUCAAAmAmGmU*mG*A*A*C 4 cp-asiAR72 AS(2, 4) AUUAGCAGGUCAAAmAmGU*G*A*A*C 5 cp-asiAR78 S mGCmUGmCAmUCmAGtaUOmCAm*C*U*chol 6 cp-asiAR78 AS (7, 4) AGUGAACUGAUGCAmGmCmU*mC*mO*mC*mU 7 cp-asiAR78 AS (4, 4) AGUGAACUGAUGCAmGmCmU*mC*U*C*U 8 cp-asiAR78 AS (2, 4) AGUGAACUGAUGCAmGmCU*C*U*C*U 9 cp-asiARI10 S niGCmCCniAUmGrumUAmGCmUUni*A*U*chol 10 cp-asiARHO AS (7,4) AUAAGCUAACAUGGmGmCmA*mC*mtt*mA*mG 11 cp-asiARHO AS (4,4) AUAAGCUAACAUGGmGmCmA*mC*U*A*G 12 cp-asiARHO AS (2,4) AUAAGCUAACAUGGmGaCA*C*U*A*G m : 2 -O-Methyl RNA, * : phosphorothioated bond, chol :cholesterol [Example 13] Screening for cp-asiRNA Targeting AR Gene and Having Self Cell-Penetrating Ability 5 The inhibitory effects of the 9 kinds of cp-asiRNA shown in Table 8 against AR expression were examined. An A549 cell line was incubated with 1 pM or 3 pM of each of the 9 cpasiRNAs in Opti-MEM media for 24 hours, and then the media were replaced with Dulbecco's Modified Eagle's Medium (Gibco) 10 containing 10% fetal bovine serum (Gibco) and 100 units/ml penicillin 100 pg/ml streptomycin, and after 24 hours, AR expression was examined at the mRNA level. As the result of repeatedly conducting four experiments, it was confirmed that the 9 kinds of AR cp-asiRNA exhibited gene inhibitory 15 efficiency of 50% at a concentration of 3 pM (see FIG. 13). Under the same experimental conditions, the inhibitory effects of the 9 kinds of cp-asiRNA against AR expression were examined at the protein level in an A549 cell line. The A549 cell line was incubated with 1 pM or 3 pM of each of the 9 cp- 605 10 15 20 25 CA 03054001 2019-08-19 asiRNAs in Opti-MEM media for 24 hours, and then the media were replaced with Dulbecco's Modified Eagle's Medium (Gibco) containing 10% fetal bovine serum (Gibco) and 100 units/ml penicillin 100 pg/ml streptomycin, and after 24 hours, AR expression was examined at the protein level. Among them, cpasiRNA #72(7,4), #78(7,4)(4,4)(2,4), and #110(7,4)(4,4) exhibited target gene protein expression inhibitory efficiency of 50% or higher at a concentration of 1 pM on the basis of the band intensity of a no treatment (NT) sample and a 1/2 NT sample (see FIG. 14). While the present invention has been described in detail with reference to specific embodiments thereof, it will be obvious to those of ordinary skill in the art that these embodiments are provided for illustrative purposes only and are not intended to limit the scope of the present invention. Therefore, the actual scope of the present invention will be defined by the appended claims and equivalents thereof. [industrial Applicability] A 5a-reductase type 1-encoding gene, a 5a-reductase type 2-encoding gene, and an androgen receptor-encoding gene, which play a major role in inhibiting the synthesis of proteins required for hair follicle growth in male pattern hair loss and inducing hair loss by reducing the size of the dermal papilla, were selected as target genes, and asymmetric siRNA with high inhibitory efficiency against each target gene was 61CA 03054001 2019-08-19 selected. siRNA according to the present invention exhibits the ability to inhibit the expression of the target gene for 5a-reductase type 1, 5a-reductase type 2, or an androgen receptor, and thus may be effectively used as an agent for 5 preventing or treating hair loss. While the present invention has been particularly shown and described with reference to specific embodiments thereof, it will be obvious to those of ordinary skill in the art that 10 such embodiments are provided for illustrative purposes only and are not intended to limit the scope of the present invention. Therefore, the actual scope of the present invention should be defined by the appended claims and equivalents thereof. 15 [Sequence List Free Text] Electronic files attached. 62