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US20020192826A1 - Recombinant AAV vector-based transduction system and use of same - Google Patents

Recombinant AAV vector-based transduction system and use of same Download PDF

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Publication number
US20020192826A1
US20020192826A1 US10/218,280 US21828002A US2002192826A1 US 20020192826 A1 US20020192826 A1 US 20020192826A1 US 21828002 A US21828002 A US 21828002A US 2002192826 A1 US2002192826 A1 US 2002192826A1
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rep
cells
transduction system
dna
aav
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Gerd Maass
Christoph Bogedain
Michael Hallek
Clemens Wendtner
Doris Michl
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Definitions

  • the present invention relates to a transduction system which comprises a rep-negative AAV vector and its use.
  • transduction The transfer of genes by means of viruses as a vector is referred to as transduction.
  • Transduction is frequently used to integrate genes into the genome of cells.
  • adeno-associated viruses AAVs are used as viruses for this purpose.
  • AAVs are single-stranded DNA viruses belonging to the Parvorirus family.
  • AAVs require helper viruses, particularly adenoviruses or herpesviruses, for their replication.
  • helper viruses In the absence of helper viruses AAVs integrate into the host cell genome, particularly at a specific site on chromosome 19 .
  • the genome of AAVs is linear and has a length of about 4680 nucleotides. It comprises two reading frames which code for a structural gene and a non-structural gene.
  • the structural gene is referred to as cap gene. It is controlled by the P40 promoter and codes for three capsid proteins.
  • the non-structural gene is referred to as the rep gene and codes for the rep proteins, Rep 78, Rep 68, Rep 52 and Rep 40.
  • the two former proteins are expressed under the control of the P5 promoter while the expression of Rep 52 and Rep 40 is controlled by the P19 promoter.
  • the functions of the Rep proteins are represented inter alia by the control of replication and transcription of the AAV genome.
  • AAVs recombinant AAVs
  • AAVs containing foreign DNA often do not integrate into the genome of cells, so that the foreign DNA is not transferred either.
  • the latter is important and largely indispensable for manipulating cells, particularly for gene therapy.
  • the present invention provides a transduction system, comprising:
  • the present invention is based on the discovery that AAVs lacking a rep gene do not integrate into the genome of cells.
  • rep-negative AAV vector relates to any AAV, i.e., virus particle, and the DNA thereof, which are rep-negative. This means that no rep gene or only a defective rep gene is present.
  • Conventional methods can be used for providing a rep-negative AAV vector. For example, an AAV DNA can be modified by specific mutagenesis in the rep gene such that it becomes defective or the rep gene is deleted by special restriction cleavage and ligation.
  • a rep-negative AAV DNA can then be transferred into cells which express an AAV-rep gene, and rep-negative AAVs, i.e., virus particules, are obtained after infection with a helper virus.
  • the term “foreign DNA” includes any DNA that can be integrated into a rep-negative AAV vector.
  • the foreign DNA may be non-coding or coding.
  • the foreign DNA can be a regulator element of the DNA replication and/or transcription.
  • the foreign DNA can code for a diagnostic and/or therapeutic protein. Examples of therapeutic proteins include tumor necrosis factor, interferons, interleukins, lymphokines, growth factors, plasma proteins and receptors.
  • the foreign DNA can be inserted at any site on the rep-negative AAV vector. It may be advantageous for the foreign DNA to be present in or in place of the rep gene. Furthermore, in some embodiments, several foreign DNAs are present.
  • a product providing an AAV-Rep protein includes any product which can provide an AAV Rep protein, particularly Rep 78 or Rep 68, or a portion thereof.
  • the product may be a DNA (rep-DNA) adapted to express an AAV Rep protein and a portion thereof, respectively.
  • the expression of the rep-DNA may be controlled by an inducible promoter such as an antibiotic-specific or tissue-specific promoter.
  • the rep-DNA may be provided by the genome of an AAV virus particle. It is preferable for the genome to have a defective (deleted) cap gene and an inducible promoter for the cap gene, respectively, and/or one or more defective (deleted) ITR sequences.
  • the genome and the corresponding AAV virus particle may also be a product within the meaning of the term.
  • the product may be an AAV Rep protein, particularly Rep 78 or Rep 68, or a portion thereof and a fusion protein that contains an AAV Rep protein or a portion thereof.
  • Such proteins can be provided by conventional methods.
  • Components (a) and (b) may be connected with each other in a transduction system according to the present invention. Such a connection may be made by conventional methods.
  • the AAV vector of component (a) is present as a virus particle and the product of component (b) is available as rep-expressing DNA, it may be preferred to proceed in the following manner:
  • the AAV vector may be modified chemically or enzymatically.
  • it may be biotinylated, i.e., biotin or a biotinylated anti-AAV antibody such as an antibody directed against the AAV proteins VP-1, VP-2 or VP-3 may be bound to an AAV vector.
  • the rep-expressing DNA may be mixed with DNA-binding substances such as organic polycations, e.g., polylysine and/or polyornithine, and heterologous polycations having several differing, positively charged amino acids, respectively.
  • Such a transduction system is suitable for the transduction of cells.
  • the cells may be of any type or origin.
  • the cells may be present separately or in aggregation such as in a tissue or an organ.
  • the cells may also be present within or outside an organism. In the latter case, the cells may be held in culture.
  • the cells may be healthy cells, diseased cells such as virus-infected cells or cells affected by microorganisms or protozoa, or tumor cells.
  • the cells may be transduced by common methods. If a transduction system is used wherein components (a) and (b) are connected with each other and the AAV vector and/or the product is present as a virus particle, the cells can be infected with the transduction system. However, if the AAV vector and the product are present as DNA, the transduction system can be introduced into the cells, e.g., by transfection, lipofection or electroporation.
  • the cells can be infected with the virus particles.
  • the AAV vector is present as a virus particle and the product as DNA or vice versa, the cells may be infected with the AAV vector and the product.
  • the DNA can be introduced into the cells as described above.
  • the AAV vector and the product are each present as DNA, they can be introduced into the cells as described above.
  • the product is present in the form of an AAV Rep protein or as a portion thereof or as a fusion protein containing an AAV Rep protein or a portion thereof, the product may be introduced into the cells by lipofection.
  • the present invention provides a means to integrate foreign DNA into the genome of cells.
  • a specific site on chromosome 19 is frequently used as a site of integration. Additionally, the tissue-specific expression of the foreign DNA is possible.
  • the AAV Rep protein may be provided only temporarily to the transduced cells. This may have favorable influences on the cells.
  • the present invention is not limited to certain cells or to certain cellular environments.
  • the present invention can be used for transducing cells that are within an organism or outside an organism.
  • the present invention is perfectly suited to transduce cells of a withdrawn tumor material without these cells having to be cultured beforehand.
  • the present invention is suited for use in gene therapy, particularly of monogenic diseases such as hemoglobin anomalies, cystic fibrosis, subtypes of Parkinson's disease and hemophilias, AIDS and cancers.
  • the transduction system according to the invention that is used is one wherein components (a) and (b) are separate from each other.
  • the transfected cells are then infected with a rep-negative AAV vector, i.e., a virus particle containing an expressible foreign DNA; e.g., a DNA coding for a B7 protein.
  • a rep-negative AAV vector i.e., a virus particle containing an expressible foreign DNA; e.g., a DNA coding for a B7 protein.
  • a specific integration of the foreign DNA is obtained at chromosome 19. This is proved by common methods.
  • expression of the B7 protein is obtained. This is proved by an antibody directed against the B7 protein.
  • One, pUHD15-1 codes for the fusion protein tetR-VP16 (cf. Gossen, M. et al., PNAS USA 89 (1992), 5547-5551).
  • tetR is a tetracycline repressor while VP16 is the transactivation domain of the VP16 molecule of HSV.
  • the second expression plasmid, pUHD10-3 contains an AAV-rep gene which is controlled by a promoter that is induced by the fusion protein tetR-VP16. This induction is obtained when tetracycline is removed from the medium.
  • the detection of transfection is determined via the expression of a neomycin resistance gene on the first expression plasmid and the expression of the rep gene on the second expression plasmid.
  • the transfected cells are then infected with the rep-negative AAV vector of (a) containing a foreign DNA coding for a B7 protein. Having removed tetracycline from the medium, a specific integration of the foreign DNA is obtained at chromosome 19. This is proved by common methods. Moreover, an expression of the B7 protein is obtained. This is proved by an antibody directed against the B7 protein.

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Abstract

The present invention relates to a transduction system, comprising (a) a rep-negative AAV vector containing a foreign DNA and (b) a product providing an AAV Rep protein. The invention also relates to the use of the transduction system.

Description

  • This application is a continuation of U.S. application Ser. No. 09/773,302, filed Jan. 30, 2001; which is a continuation of U.S. application Ser. No. 09/142,389, filed May 5, 1999, now U.S. Pat. No. 6,207,453; which was the National Stage of International Application No. PCT/DE97/00447, filed Mar. 6, 1997; which claims the priority of Germany Application 196 08 753.8, filed Mar. 6, 1996.[0001]
    • FIELD OF THE INVENTION
  • The present invention relates to a transduction system which comprises a rep-negative AAV vector and its use. [0002]
    • BACKGROUND OF THE INVENTION
  • The transfer of genes by means of viruses as a vector is referred to as transduction. Transduction is frequently used to integrate genes into the genome of cells. For example, adeno-associated viruses (AAVs) are used as viruses for this purpose. [0003]
  • AAVs are single-stranded DNA viruses belonging to the Parvorirus family. AAVs require helper viruses, particularly adenoviruses or herpesviruses, for their replication. In the absence of helper viruses AAVs integrate into the host cell genome, particularly at a specific site on chromosome [0004] 19.
  • The genome of AAVs is linear and has a length of about 4680 nucleotides. It comprises two reading frames which code for a structural gene and a non-structural gene. The structural gene is referred to as cap gene. It is controlled by the P40 promoter and codes for three capsid proteins. The non-structural gene is referred to as the rep gene and codes for the rep proteins, Rep 78, Rep 68, Rep 52 and Rep 40. The two former proteins are expressed under the control of the P5 promoter while the expression of Rep 52 and Rep 40 is controlled by the P19 promoter. The functions of the Rep proteins are represented inter alia by the control of replication and transcription of the AAV genome. [0005]
  • It has now been determined that recombinant AAVs, i.e., AAVs containing foreign DNA, often do not integrate into the genome of cells, so that the foreign DNA is not transferred either. However, the latter is important and largely indispensable for manipulating cells, particularly for gene therapy. [0006]
  • It is an object of the present invention to provide a product by which a foreign DNA can be integrated into the genome of cells in an effective manner. According to the invention, this is achieved by the subject matter defined in the claims. [0007]
    • BRIEF SUMMARY OF THE INVENTION
  • Thus, the present invention provides a transduction system, comprising: [0008]
  • (a) a rep-negative AAV vector containing a foreign DNA, and [0009]
  • (b) a product providing an AAV Rep protein. [0010]
    • DETAILED DESCRIPTION OF THE INVENTION
  • The present invention is based on the discovery that AAVs lacking a rep gene do not integrate into the genome of cells. [0011]
  • The term “rep-negative AAV vector” relates to any AAV, i.e., virus particle, and the DNA thereof, which are rep-negative. This means that no rep gene or only a defective rep gene is present. Conventional methods can be used for providing a rep-negative AAV vector. For example, an AAV DNA can be modified by specific mutagenesis in the rep gene such that it becomes defective or the rep gene is deleted by special restriction cleavage and ligation. A rep-negative AAV DNA can then be transferred into cells which express an AAV-rep gene, and rep-negative AAVs, i.e., virus particules, are obtained after infection with a helper virus. [0012]
  • The term “foreign DNA” includes any DNA that can be integrated into a rep-negative AAV vector. The foreign DNA may be non-coding or coding. In the case of non-coding DNA, the foreign DNA can be a regulator element of the DNA replication and/or transcription. In the case of coding DNA, it is preferable for the foreign DNA to be expressible. It is especially preferred that the expression be controlled by an inducible promoter such as a tissue-specific promoter. In addition, the foreign DNA can code for a diagnostic and/or therapeutic protein. Examples of therapeutic proteins include tumor necrosis factor, interferons, interleukins, lymphokines, growth factors, plasma proteins and receptors. In addition, the foreign DNA can be inserted at any site on the rep-negative AAV vector. It may be advantageous for the foreign DNA to be present in or in place of the rep gene. Furthermore, in some embodiments, several foreign DNAs are present. [0013]
  • The term “a product providing an AAV-Rep protein” includes any product which can provide an AAV Rep protein, particularly Rep 78 or Rep 68, or a portion thereof. For example, the product may be a DNA (rep-DNA) adapted to express an AAV Rep protein and a portion thereof, respectively. It is preferable for the expression of the rep-DNA to be controlled by an inducible promoter such as an antibiotic-specific or tissue-specific promoter. The rep-DNA may be provided by the genome of an AAV virus particle. It is preferable for the genome to have a defective (deleted) cap gene and an inducible promoter for the cap gene, respectively, and/or one or more defective (deleted) ITR sequences. The genome and the corresponding AAV virus particle may also be a product within the meaning of the term. In addition, the product may be an AAV Rep protein, particularly Rep 78 or Rep 68, or a portion thereof and a fusion protein that contains an AAV Rep protein or a portion thereof. Such proteins can be provided by conventional methods. [0014]
  • Components (a) and (b) may be connected with each other in a transduction system according to the present invention. Such a connection may be made by conventional methods. For example, if the AAV vector of component (a) is present as a virus particle and the product of component (b) is available as rep-expressing DNA, it may be preferred to proceed in the following manner: The AAV vector may be modified chemically or enzymatically. For example, it may be biotinylated, i.e., biotin or a biotinylated anti-AAV antibody such as an antibody directed against the AAV proteins VP-1, VP-2 or VP-3 may be bound to an AAV vector. The rep-expressing DNA may be mixed with DNA-binding substances such as organic polycations, e.g., polylysine and/or polyornithine, and heterologous polycations having several differing, positively charged amino acids, respectively. [0015]
  • It is especially preferred to mix the rep-expressing DNA with polylysine and streptavidin so that polylysine binds to the DNA and streptavidine binds to the polylysine. The biotinylated AAV vector and the streptavidine-polylysine-modified DNA are then mixed, so that the bond between components (a) and (b) is formed. [0016]
  • Such a transduction system is suitable for the transduction of cells. The cells may be of any type or origin. Furthermore, the cells may be present separately or in aggregation such as in a tissue or an organ. The cells may also be present within or outside an organism. In the latter case, the cells may be held in culture. Moreover, the cells may be healthy cells, diseased cells such as virus-infected cells or cells affected by microorganisms or protozoa, or tumor cells. [0017]
  • The cells may be transduced by common methods. If a transduction system is used wherein components (a) and (b) are connected with each other and the AAV vector and/or the product is present as a virus particle, the cells can be infected with the transduction system. However, if the AAV vector and the product are present as DNA, the transduction system can be introduced into the cells, e.g., by transfection, lipofection or electroporation. [0018]
  • If a transduction system is used wherein components (a) and (b) are not connected with each other, and the AAV vector and the product are present as a virus particle, the cells can be infected with the virus particles. However, if the AAV vector is present as a virus particle and the product as DNA or vice versa, the cells may be infected with the AAV vector and the product. The DNA can be introduced into the cells as described above. [0019]
  • Furthermore, if the AAV vector and the product are each present as DNA, they can be introduced into the cells as described above. Moreover, if the product is present in the form of an AAV Rep protein or as a portion thereof or as a fusion protein containing an AAV Rep protein or a portion thereof, the product may be introduced into the cells by lipofection. [0020]
  • The present invention provides a means to integrate foreign DNA into the genome of cells. A specific site on chromosome 19 is frequently used as a site of integration. Additionally, the tissue-specific expression of the foreign DNA is possible. Moreover, the AAV Rep protein may be provided only temporarily to the transduced cells. This may have favorable influences on the cells. [0021]
  • In addition, the present invention is not limited to certain cells or to certain cellular environments. The present invention can be used for transducing cells that are within an organism or outside an organism. In particular, the present invention is perfectly suited to transduce cells of a withdrawn tumor material without these cells having to be cultured beforehand. [0022]
  • Therefore, the present invention is suited for use in gene therapy, particularly of monogenic diseases such as hemoglobin anomalies, cystic fibrosis, subtypes of Parkinson's disease and hemophilias, AIDS and cancers. [0023]
  • The following example is provided to illustrate the invention. However, the invention is not limited thereby.[0024]
    • EXAMPLE 1 Transduction of Cells
  • The transduction system according to the invention that is used is one wherein components (a) and (b) are separate from each other. [0025]
  • (a) Cells of the human cervical carcinoma line HeLa are transfected with an expression plasmid pRc/CMV (Invitrogen) which contains an AAV-rep gene under the control of the CMV promoter. In preliminary tests using such an expression plasmid it was shown that a transfection efficiency of 30 to 60% can be achieved. The expression of the AAV-rep gene is determined in the immunoblot by an antibody directed against AAV-Rep 78. [0026]
  • The transfected cells are then infected with a rep-negative AAV vector, i.e., a virus particle containing an expressible foreign DNA; e.g., a DNA coding for a B7 protein. A specific integration of the foreign DNA is obtained at chromosome 19. This is proved by common methods. Moreover, expression of the B7 protein is obtained. This is proved by an antibody directed against the B7 protein. [0027]
  • (b) Cells of the human cervical carcinoma line HeLa are transfected with two expression plasmids. One, pUHD15-1, codes for the fusion protein tetR-VP16 (cf. Gossen, M. et al., [0028] PNAS USA 89 (1992), 5547-5551). tetR is a tetracycline repressor while VP16 is the transactivation domain of the VP16 molecule of HSV. The second expression plasmid, pUHD10-3, contains an AAV-rep gene which is controlled by a promoter that is induced by the fusion protein tetR-VP16. This induction is obtained when tetracycline is removed from the medium. The detection of transfection is determined via the expression of a neomycin resistance gene on the first expression plasmid and the expression of the rep gene on the second expression plasmid.
  • The transfected cells are then infected with the rep-negative AAV vector of (a) containing a foreign DNA coding for a B7 protein. Having removed tetracycline from the medium, a specific integration of the foreign DNA is obtained at chromosome 19. This is proved by common methods. Moreover, an expression of the B7 protein is obtained. This is proved by an antibody directed against the B7 protein. [0029]
  • The above data demonstrate that a transduction system according to the invention is capable of integrating a foreign DNA specifically into the genome of cells. [0030]
  • The invention having been described in detail, the scope of the invention is limited only by the appended claims. [0031]

Claims (16)

What is claimed is:
1. A transduction system comprising:
(a) a rep-negative AAV vector containing a foreign DNA; and
(b) a product providing an AAV Rep protein.
2. The transduction system according to claim 1, wherein the rep-negative AAV vector is present as DNA.
3. The transduction system according to claim 1, wherein the foreign DNA is expressible.
4. The transduction system according to claim 3, wherein the foreign DNA is controlled by an inducible promoter.
5. The transduction system according to claim 1, wherein the product is an expressible rep-DNA.
6. The transduction system according to claim 5, wherein the rep-DNA is controlled by an inducible promoter.
7. The transduction system according to claims 5 or 6, wherein the rep-DNA is provided within the genome of an AAV virus particle.
8. The transduction system according to claim 7, wherein the genome contains a defective cap gene or a deleted cap gene.
9. The transduction system according to claim 7, wherein the genome contains at least one defective ITR sequence.
10. The transduction system according to claim 1, wherein the product is an AAV Rep protein.
11. The transduction system according to claim 1, wherein the AAV vector is connected with the product.
12. A method for transducting cells comprising the step of introducing a tranduction system into the cells according to claim 1.
13. The method of claim 11, wherein the cells are determined for gene therapy.
14. The method of claim 11, wherein the cells are healthy, diseased or tumor cells.
15. The method of claim 11, wherein the cells are present in an organism.
16. The method of claim 11, wherein the cells are located outside an organism.
US10/218,280 1996-03-06 2002-08-12 Recombinant AAV vector-based transduction system and use of same Abandoned US20020192826A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US10/218,280 US20020192826A1 (en) 1996-03-06 2002-08-12 Recombinant AAV vector-based transduction system and use of same

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
DE19608753A DE19608753C1 (en) 1996-03-06 1996-03-06 Transduction system based on rep-negative adeno-associated virus vector
DE19608753.8 1996-03-06
DEPCT/DE97/00447 1997-03-06
PCT/DE1997/000447 WO1997032989A2 (en) 1996-03-06 1997-03-06 Recombinant aav vector-based transduction system and use of same
US09/142,289 US6207453B1 (en) 1996-03-06 1997-03-06 Recombinant AAV vector-based transduction system and use of same
US09/773,302 US6440742B1 (en) 1996-03-06 2001-01-31 Recombinant AAV vector-based transduction system and use of same
US10/218,280 US20020192826A1 (en) 1996-03-06 2002-08-12 Recombinant AAV vector-based transduction system and use of same

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070032570A1 (en) * 2003-11-11 2007-02-08 Canon Kabushiki Kaisha Ink comprising a block copolymer dispersing agent having a hydrophilic and a hydrophobic segment and an ink-applying process and apparatus using the same

Families Citing this family (201)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19608753C1 (en) * 1996-03-06 1997-06-26 Medigene Gmbh Transduction system based on rep-negative adeno-associated virus vector
DE60334250D1 (en) * 2003-05-08 2010-10-28 Life Technologies Corp GENERATION AND ISOLATION OF ANTIGEN-SPECIFIC T CELLS
WO2006033689A2 (en) * 2004-06-18 2006-03-30 The University Of Montana Aav mediated gene delivery to cochlear cells
US20100080784A1 (en) * 2008-09-12 2010-04-01 Torrey Pines Institute For Molecular Studies Methods for treating cachexia and lymphopenia
WO2013163628A2 (en) 2012-04-27 2013-10-31 Duke University Genetic correction of mutated genes
US9828582B2 (en) 2013-03-19 2017-11-28 Duke University Compositions and methods for the induction and tuning of gene expression
BR112016024579A2 (en) 2014-04-23 2017-10-10 Juno Therapeutics Inc Methods for Isolation, Culture, and Genetic Engineering of Immune Cell Populations for Foster Therapy
CA2954414A1 (en) 2014-07-15 2016-01-21 Juno Therapeutics, Inc. Engineered cells for adoptive cell therapy
TWI805109B (en) 2014-08-28 2023-06-11 美商奇諾治療有限公司 Antibodies and chimeric antigen receptors specific for cd19
US10507219B2 (en) 2014-10-20 2019-12-17 Juno Therapeutics, Inc. Methods and compositions for dosing in adoptive cell therapy
EP3757206B1 (en) 2014-11-05 2024-04-10 Juno Therapeutics, Inc. Methods for transduction and cell processing
ES2987087T3 (en) 2014-12-03 2024-11-13 Juno Therapeutics Inc Methods and compositions for adoptive cell therapy
CA2973964A1 (en) 2015-01-16 2016-07-21 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for ror1
US10676726B2 (en) 2015-02-09 2020-06-09 Duke University Compositions and methods for epigenome editing
WO2016166568A1 (en) 2015-04-16 2016-10-20 Juno Therapeutics Gmbh Methods, kits and apparatus for expanding a population of cells
EP3303586A1 (en) 2015-05-29 2018-04-11 Juno Therapeutics, Inc. Composition and methods for regulating inhibitory interactions in genetically engineered cells
MA42895A (en) 2015-07-15 2018-05-23 Juno Therapeutics Inc MODIFIED CELLS FOR ADOPTIVE CELL THERAPY
WO2017066497A2 (en) 2015-10-13 2017-04-20 Duke University Genome engineering with type i crispr systems in eukaryotic cells
MA45488A (en) 2015-10-22 2018-08-29 Juno Therapeutics Gmbh CELL CULTURE PROCESSES, KITS AND APPARATUS
MA45489A (en) 2015-10-22 2018-08-29 Juno Therapeutics Gmbh CELL CULTURE PROCESSES, ASSOCIATED KITS AND APPARATUS
US11020429B2 (en) 2015-11-05 2021-06-01 Juno Therapeutics, Inc. Vectors and genetically engineered immune cells expressing metabolic pathway modulators and uses in adoptive cell therapy
MA44314A (en) 2015-11-05 2018-09-12 Juno Therapeutics Inc CHEMERICAL RECEPTORS CONTAINING TRAF-INDUCING DOMAINS, AND ASSOCIATED COMPOSITIONS AND METHODS
KR20250044471A (en) 2015-11-30 2025-03-31 듀크 유니버시티 Therapeutic targets for the correction of the human dystrophin gene by gene editing and methods of use
WO2017096327A2 (en) 2015-12-03 2017-06-08 Juno Therapeutics, Inc. Compositions and methods for reducing immune responses against cell therapies
CA3007262A1 (en) 2015-12-03 2017-06-08 Lucas James Thompson Modified chimeric receptors and related compositions and methods
WO2017096331A1 (en) 2015-12-04 2017-06-08 Juno Therapeutics, Inc. Methods and compositions related to toxicity associated with cell therapy
MA43759A (en) 2016-03-16 2018-11-28 Jason Connor PROCESSES FOR THE ADAPTIVE DESIGN OF A TREATMENT REGIME AND ASSOCIATED TREATMENTS
EP3430548A1 (en) 2016-03-16 2019-01-23 Juno Therapeutics, Inc. Methods for determining dosing of a therapeutic agent and related treatments
JP7048571B2 (en) 2016-03-22 2022-04-05 シアトル チルドレンズ ホスピタル （ディービーエイ シアトル チルドレンズ リサーチ インスティテュート） Early intervention to prevent or improve toxicity
WO2017180915A2 (en) 2016-04-13 2017-10-19 Duke University Crispr/cas9-based repressors for silencing gene targets in vivo and methods of use
MA44869A (en) 2016-05-06 2019-03-13 Editas Medicine Inc GENETICALLY MODIFIED CELLS AND THEIR MANUFACTURING PROCESSES
CA3026453A1 (en) 2016-06-03 2017-12-07 Memorial Sloan-Kettering Cancer Center Adoptive cell therapies as early treatment options
MA45341A (en) 2016-06-06 2019-04-10 Hutchinson Fred Cancer Res METHODS FOR TREATING B-LYMPHOCYTE MALIGNITIES USING ADOPTIVE CELL THERAPY
MA45491A (en) 2016-06-27 2019-05-01 Juno Therapeutics Inc CMH-E RESTRICTED EPITOPES, BINDING MOLECULES AND RELATED METHODS AND USES
CN110291402B (en) 2016-06-27 2023-09-01 朱诺治疗学股份有限公司 Methods of identifying peptide epitopes, molecules that bind such epitopes, and related uses
JP7490211B2 (en) 2016-07-19 2024-05-27 デューク ユニバーシティ Therapeutic Applications of CPF1-Based Genome Editing
KR20230107408A (en) 2016-07-29 2023-07-14 주노 쎄러퓨티크스 인코퍼레이티드 Anti-idiotypic antibodies against anti-cd19 antibodies
CA3031955A1 (en) 2016-07-29 2018-02-01 Juno Therapeutics, Inc. Immunomodulatory polypeptides and related compositions and methods
BR112019004662A2 (en) 2016-09-12 2019-05-28 Juno Therapeutics Inc infusion bioreactor bag sets
WO2018063985A1 (en) 2016-09-28 2018-04-05 Atossa Genetics Inc. Methods of adoptive cell therapy
EP3519433A1 (en) 2016-10-03 2019-08-07 Juno Therapeutics, Inc. Hpv-specific binding molecules
MA50839A (en) 2016-10-13 2019-08-21 Juno Therapeutics Inc METHODS AND COMPOSITIONS OF IMMUNOTHERAPY INVOLVING MODULATORS OF THE TRYPTOPHAN METABOLIC PATHWAY
CN110139669A (en) 2016-11-03 2019-08-16 朱诺治疗学股份有限公司 The combination treatment of T cell therapy and BTK inhibitor
CA3040914A1 (en) 2016-11-03 2018-05-24 Juno Therapeutics, Inc. Combination therapy of a cell based therapy and a microglia inhibitor
US11793833B2 (en) 2016-12-02 2023-10-24 Juno Therapeutics, Inc. Engineered B cells and related compositions and methods
US11590167B2 (en) 2016-12-03 2023-02-28 Juno Therapeutic, Inc. Methods and compositions for use of therapeutic T cells in combination with kinase inhibitors
ES2961666T3 (en) 2016-12-03 2024-03-13 Juno Therapeutics Inc Methods to determine CAR-T cell dosage
BR112019011025A2 (en) 2016-12-03 2019-10-08 Juno Therapeutics Inc T cell modulation methods
CN110418802A (en) 2017-01-20 2019-11-05 朱诺治疗学有限公司 Cell surface conjugate and relevant cell composition and method
IL268349B2 (en) 2017-02-17 2024-08-01 Hutchinson Fred Cancer Res Combination therapies for the treatment of BCMA-associated cancer and autoimmune disorders
EP3585402B1 (en) 2017-02-27 2024-03-06 Juno Therapeutics, Inc. Compositions, articles of manufacture and methods related to dosing in cell therapy
WO2018170188A2 (en) 2017-03-14 2018-09-20 Juno Therapeutics, Inc. Methods for cryogenic storage
JOP20180027A1 (en) 2017-03-28 2019-01-30 Cell Design Labs Inc Chimeric polypeptides and methods of altering the membrane localization of the same
EP3607319A1 (en) 2017-04-07 2020-02-12 Juno Therapeutics, Inc. Engineered cells expressing prostate-specific membrane antigen (psma) or a modified form thereof and related methods
AU2018251188A1 (en) 2017-04-14 2019-10-31 Juno Therapeutics, Inc. Methods for assessing cell surface glycosylation
SG11201909931PA (en) 2017-04-27 2019-11-28 Juno Therapeutics Gmbh Oligomeric particle reagents and methods of use thereof
EP3618842B1 (en) 2017-05-01 2023-10-18 Juno Therapeutics, Inc. Combination of a cell therapy and an immunomodulatory compound
US11740231B2 (en) 2017-06-02 2023-08-29 Juno Therapeutics, Inc. Articles of manufacture and methods related to toxicity associated with cell therapy
CN111225675B (en) 2017-06-02 2024-05-03 朱诺治疗学股份有限公司 Articles and methods of treatment using adoptive cell therapy
DK3538645T3 (en) 2017-06-20 2021-04-19 Inst Curie IMMUNE CELLS MISSING SUV39H1
AU2018291032A1 (en) 2017-06-29 2020-01-16 Juno Therapeutics, Inc. Mouse model for assessing toxicities associated with immunotherapies
BR112020001719A2 (en) 2017-07-29 2020-07-21 Juno Therapeutics Inc reagents for cell expansion that express recombinant receptors
MA49981A (en) 2017-08-09 2020-06-17 Juno Therapeutics Inc PROCESSES AND COMPOSITIONS FOR THE PREPARATION OF GENETICALLY MODIFIED CELLS
BR112020001605A2 (en) 2017-08-09 2020-08-11 Juno Therapeutics Inc methods for producing genetically modified cell compositions and related compositions
EP3676403A1 (en) 2017-09-01 2020-07-08 Juno Therapeutics, Inc. Gene expression and assessment of risk of developing toxicity following cell therapy
EP3679370A1 (en) 2017-09-07 2020-07-15 Juno Therapeutics, Inc. Methods of identifying cellular attributes related to outcomes associated with cell therapy
EP3692063A1 (en) 2017-10-03 2020-08-12 Juno Therapeutics, Inc. Hpv-specific binding molecules
WO2019089982A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Method of assessing activity of recombinant antigen receptors
BR112020008565A2 (en) 2017-11-01 2020-10-20 Juno Therapeutics Inc process for producing a t cell composition
WO2019089848A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Methods associated with tumor burden for assessing response to a cell therapy
EP3704251A2 (en) 2017-11-01 2020-09-09 Editas Medicine, Inc. Methods, compositions and components for crispr-cas9 editing of tgfbr2 in t cells for immunotherapy
CA3080904A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for b-cell maturation antigen
US12258580B2 (en) 2017-11-01 2025-03-25 Juno Therapeutics, Inc. Process for generating therapeutic compositions of engineered cells
US12031975B2 (en) 2017-11-01 2024-07-09 Juno Therapeutics, Inc. Methods of assessing or monitoring a response to a cell therapy
JP7447006B2 (en) 2017-11-01 2024-03-11 ジュノー セラピューティクス インコーポレイテッド Chimeric antigen receptor specific for B cell maturation antigen (BCMA)
US20230137729A1 (en) 2017-11-06 2023-05-04 Editas Medicine, Inc. Methods, compositions and components for crispr-cas9 editing of cblb in t cells for immunotherapy
JP7233425B2 (en) 2017-11-06 2023-03-06 ジュノー セラピューティクス インコーポレイテッド Combination of cell therapy and gamma secretase inhibitor
CN111556789A (en) 2017-11-10 2020-08-18 朱诺治疗学股份有限公司 Closed System Cryogenic Vessels
EP3716980A1 (en) 2017-12-01 2020-10-07 Juno Therapeutics, Inc. Methods for dosing and for modulation of genetically engineered cells
MX2020005908A (en) 2017-12-08 2020-10-07 Juno Therapeutics Inc Process for producing a composition of engineered t cells.
BR112020011223A2 (en) 2017-12-08 2020-11-17 Juno Therapeutics Inc phenotypic markers for cell therapy and related methods
MA51105A (en) 2017-12-08 2020-10-14 Juno Therapeutics Inc FORMULATION OF SERUM-FREE MEDIA FOR CELL CULTURE AND METHODS OF USE
JP2021506260A (en) 2017-12-15 2021-02-22 ジュノー セラピューティクス インコーポレイテッド Anti-CCT5 binding molecule and how to use it
WO2019126358A1 (en) 2017-12-22 2019-06-27 Cell Design Labs, Inc. Single- and multi-chain chimeric antigen receptors
WO2019144061A1 (en) 2018-01-19 2019-07-25 Duke University Genome engineering with crispr-cas systems in eukaryotes
JP7383620B2 (en) 2018-01-31 2023-11-20 セルジーン コーポレイション Combination therapy using adoptive cell therapy and checkpoint inhibitors
EP3762012A1 (en) 2018-03-09 2021-01-13 Ospedale San Raffaele S.r.l. Il-1 antagonist and toxicity induced by cell therapy
US12280119B2 (en) 2018-03-23 2025-04-22 Kite Pharma, Inc. Chimeric transmembrane proteins and uses thereof
MX2020010461A (en) 2018-04-05 2021-01-15 Juno Therapeutics Inc T cells expressing a recombinant receptor, related polynucleotides and methods.
KR102764123B1 (en) 2018-04-05 2025-02-05 주노 쎄러퓨티크스 인코퍼레이티드 T cell receptor and engineered cells expressing it
BR112020020245A2 (en) 2018-04-05 2021-04-06 Editas Medicine, Inc. METHODS OF PRODUCING CELLS EXPRESSING A RECOMBINANT RECEIVER AND RELATED COMPOSITIONS
BR112020022185A2 (en) 2018-05-03 2021-02-02 Juno Therapeutics Inc combination therapy of a chimeric antigen (car) receptor t cell therapy and a kinase inhibitor
JP2021527689A (en) 2018-06-22 2021-10-14 カイト ファーマ インコーポレイテッドＫｉｔｅ Ｐｈａｒｍａ， Ｉｎｃ Chimeric transmembrane protein and its use
BR112021002245A2 (en) 2018-08-09 2021-05-04 Juno Therapeutics Inc methods for evaluating integrated nucleic acids
IL280659B2 (en) 2018-08-09 2024-11-01 Juno Therapeutics Inc Processes for creating transgenic cells and their compounds
KR20210081341A (en) 2018-09-11 2021-07-01 주노 쎄러퓨티크스 인코퍼레이티드 Methods for Mass Spectrometry Analysis of Engineered Cell Compositions
JP2022520139A (en) 2018-10-12 2022-03-29 セラダプティブ インク Polypeptides containing β-tricalcium phosphate binding sequence and their use
EP3874024A1 (en) 2018-10-31 2021-09-08 Juno Therapeutics GmbH Methods for selection and stimulation of cells and apparatus for same
WO2020092848A2 (en) 2018-11-01 2020-05-07 Juno Therapeutics, Inc. Methods for treatment using chimeric antigen receptors specific for b-cell maturation antigen
EP3873937A2 (en) 2018-11-01 2021-09-08 Juno Therapeutics, Inc. Chimeric antigen receptors specific for g protein-coupled receptor class c group 5 member d (gprc5d)
KR20210100624A (en) 2018-11-06 2021-08-17 주노 쎄러퓨티크스 인코퍼레이티드 Methods of making genetically engineered T cells
US12263190B2 (en) 2018-11-08 2025-04-01 Juno Therapeutics, Inc. Methods and combinations for treatment and T cell modulation
EP3880238A1 (en) 2018-11-16 2021-09-22 Juno Therapeutics, Inc. Methods of dosing engineered t cells for the treatment of b cell malignancies
MX2021006238A (en) 2018-11-30 2021-10-01 Juno Therapeutics Inc METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY.
IL283298B2 (en) 2018-11-30 2025-03-01 Juno Therapeutics Inc Methods for dosing and treatment of b cell malignancies in adoptive cell therapy
PE20212198A1 (en) 2019-01-29 2021-11-16 Juno Therapeutics Inc ANTIBODIES AND CHIMERIC RECEPTORS OF SPECIFIC ANTIGENS TO ORPHAN RECEPTOR 1, RECEPTOR TYROSINE KINASE TYPE (ROR1)
MX2021013219A (en) 2019-05-01 2022-02-17 Juno Therapeutics Inc CELLS EXPRESSING A RECOMBINANT RECEPTOR OF A MODIFIED TGFBR2 LOCUS, RELATED POLYNUCLEOTIDES AND METHODS.
SG11202111372VA (en) 2019-05-01 2021-11-29 Juno Therapeutics Inc Cells expressing a chimeric receptor from a modified cd247 locus, related polynucleotides and methods
EP3980530A1 (en) 2019-06-07 2022-04-13 Juno Therapeutics, Inc. Automated t cell culture
JP2022537700A (en) 2019-06-12 2022-08-29 ジュノー セラピューティクス インコーポレイテッド Combination therapy with cell-mediated cytotoxic therapy and inhibitors of pro-survival BCL2 family proteins
BR112021025735A2 (en) 2019-06-21 2022-03-08 Kite Pharma Inc tgf-ss receivers and usage methods
JP7735249B2 (en) 2019-07-23 2025-09-08 ムネモ・セラピューティクス SUV39H1-deficient immune cells
US20220298222A1 (en) 2019-08-22 2022-09-22 Juno Therapeutics, Inc. Combination therapy of a t cell therapy and an enhancer of zeste homolog 2 (ezh2) inhibitor and related methods
JP7770306B2 (en) 2019-08-30 2025-11-14 ジュノー セラピューティクス インコーポレイテッド Machine learning methods for classifying cells
AU2020341454A1 (en) 2019-09-03 2022-03-10 Sana Biotechnology, Inc. CD24-associated particles and related methods and uses thereof
WO2021070956A1 (en) 2019-10-11 2021-04-15 タカラバイオ株式会社 siRNA EXPRESSION VECTOR
BR112022008023A2 (en) 2019-10-30 2022-07-12 Juno Therapeutics Gmbh CELL SELECTION AND/OR STIMULATION DEVICES AND USE METHODS
EP4055383A1 (en) 2019-11-05 2022-09-14 Juno Therapeutics, Inc. Methods of determining attributes of therapeutic t cell compositions
EP4054623A1 (en) 2019-11-07 2022-09-14 Juno Therapeutics, Inc. Combination of a t cell therapy and (s)-3-[4-(4-morpholin-4 ylmethyl-benzyloxy)-l-oxo-l,3-dihydro-isoindol-2-yl]- piperidine-2,6-dione
WO2021113776A1 (en) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to bcma-targeted binding domains and related compositions and methods
KR20220132527A (en) 2019-12-06 2022-09-30 주노 쎄러퓨티크스 인코퍼레이티드 Methods Related to Toxicity and Responses Associated with Cell Therapy for Treating Cell Malignant Tumors
WO2021113780A1 (en) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to gprc5d-targeted binding domains and related compositions and methods
IL294724A (en) 2020-01-24 2022-09-01 Juno Therapeutics Inc Methods for dosing and treatment of follicular lymphoma and marginal zone lymphoma in stress cell therapy
JP2023519099A (en) 2020-02-12 2023-05-10 ジュノー セラピューティクス インコーポレイテッド BCMA-directed chimeric antigen receptor T-cell compositions and methods and uses thereof
CN115768443A (en) 2020-02-12 2023-03-07 朱诺治疗学股份有限公司 CD19-directed chimeric antigen receptor T cell composition and method and use thereof
AU2021251265A1 (en) 2020-04-10 2022-11-03 Juno Therapeutics, Inc. Methods and uses related to cell therapy engineered with a chimeric antigen receptor targeting B-cell maturation antigen
JP2023525960A (en) 2020-04-15 2023-06-20 セラダプティブ インク Compositions and methods for delivering targeted therapeutic agents to bone
CN116157125A (en) 2020-04-28 2023-05-23 朱诺治疗学股份有限公司 T cell therapy targeting BCMA in combination with immunomodulatory compounds
US20230178239A1 (en) 2020-05-13 2023-06-08 Juno Therapeutics, Inc. Methods of identifying features associated with clinical response and uses thereof
CN115835873A (en) 2020-05-13 2023-03-21 朱诺治疗学股份有限公司 Method for producing donor batch cells expressing recombinant receptors
US20230190871A1 (en) 2020-05-20 2023-06-22 Sana Biotechnology, Inc. Methods and compositions for treatment of viral infections
JP2023531531A (en) 2020-06-26 2023-07-24 ジュノ セラピューティクス ゲーエムベーハー Engineered T Cells Conditionally Expressing Recombinant Receptors, Related Polynucleotides, and Methods
AU2021308078A1 (en) 2020-07-17 2023-02-09 Children's Hospital Los Angeles Chimeric MyD88 receptors for redirecting immunosuppressive signaling and related compositions and methods
EP4188395A1 (en) 2020-07-30 2023-06-07 Institut Curie Immune cells defective for socs1
WO2022029660A1 (en) 2020-08-05 2022-02-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to ror1-targeted binding domains and related compositions and methods
US20230303665A1 (en) 2020-08-28 2023-09-28 Sana Biotechnology, Inc. Modified anti-viral binding agents
GB202013940D0 (en) 2020-09-04 2020-10-21 Synpromics Ltd Regulatory nucleic acid sequences
CA3195177A1 (en) 2020-10-07 2022-04-14 Asklepios Biopharmaceutical, Inc. Therapeutic adeno-associated virus delivery of fukutin related protein (fkrp) for treating dystroglycanopathy disorders including limb girdle 2i (lgmd2i)
WO2022133030A1 (en) 2020-12-16 2022-06-23 Juno Therapeutics, Inc. Combination therapy of a cell therapy and a bcl2 inhibitor
AU2022206324A1 (en) 2021-01-11 2023-07-20 Sana Biotechnology, Inc. Use of cd8-targeted viral vectors
JP2024509853A (en) 2021-03-03 2024-03-05 ジュノー セラピューティクス インコーポレイテッド Combination of T cell therapy and DGK inhibitor
AU2022241654A1 (en) 2021-03-22 2023-09-28 Juno Therapeutics, Inc. Methods of determining potency of a therapeutic cell composition
JP2024514245A (en) 2021-03-29 2024-03-29 ジュノー セラピューティクス インコーポレイテッド Methods for dosing and treatment using a combination of checkpoint inhibitor therapy and CAR T cell therapy
EP4313126A1 (en) 2021-03-29 2024-02-07 Juno Therapeutics, Inc. Combination of a car t cell therapy and an immunomodulatory compound for treatment of lymphoma
JP2024514163A (en) 2021-04-16 2024-03-28 セルジーン コーポレーション Combination therapy using BCMA-directed T cell therapy
US20250283037A1 (en) 2021-05-06 2025-09-11 Juno Therapeutics Gmbh Methods for stimulating and transducing t cells
US20250304915A1 (en) 2021-05-25 2025-10-02 Institut Curie Myeloid Cells Overexpressing BCL2
AU2022291365A1 (en) 2021-06-08 2024-01-18 Kite Pharma, Inc. Gpc3 binding molecules
US20240254483A1 (en) 2021-07-30 2024-08-01 Tune Therapeutics, Inc. Compositions and methods for modulating expression of frataxin (fxn)
US20240252684A1 (en) 2021-07-30 2024-08-01 Tune Therapeutics, Inc. Compositions and methods for modulating expression of methyl-cpg binding protein 2 (mecp2)
JP2024528981A (en) 2021-08-04 2024-08-01 サナ バイオテクノロジー，インコーポレイテッド Use of CD4-targeted viral vectors
JP2024540320A (en) 2021-11-03 2024-10-31 セルジーン コーポレーション Chimeric antigen receptors specific for B cell maturation antigens for use in treating myeloma - Patent Application 20070123333
WO2023081715A1 (en) 2021-11-03 2023-05-11 Viracta Therapeutics, Inc. Combination of car t-cell therapy with btk inhibitors and methods of use thereof
WO2023081900A1 (en) 2021-11-08 2023-05-11 Juno Therapeutics, Inc. Engineered t cells expressing a recombinant t cell receptor (tcr) and related systems and methods
JP2025501272A (en) 2021-12-28 2025-01-17 ムネモ・セラピューティクス Immune cells with inactivated SUV39H1 and modified TCR
WO2023133595A2 (en) 2022-01-10 2023-07-13 Sana Biotechnology, Inc. Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses
US20250154503A1 (en) 2022-01-14 2025-05-15 Tune Therapeutics, Inc. Compositions, systems, and methods for programming t cell phenotypes through targeted gene repression
CA3247928A1 (en) 2022-01-14 2023-07-20 Tune Therapeutics, Inc. Compositions, systems, and methods for programming t cell phenotypes through targeted gene activation
EP4472646A1 (en) 2022-02-01 2024-12-11 Sana Biotechnology, Inc. Cd3-targeted lentiviral vectors and uses thereof
EP4473097A1 (en) 2022-02-02 2024-12-11 Sana Biotechnology, Inc. Methods of repeat dosing and administration of lipid particles or viral vectors and related systems and uses
AU2023223404A1 (en) 2022-02-22 2024-08-29 Juno Therapeutics, Inc. Proteinase 3 (pr3) chimeric autoantibody receptor t cells and related methods and uses
US20250222027A1 (en) 2022-04-01 2025-07-10 Sana Biotechnology, Inc. Cytokine receptor agonist and viral vector combination therapies
WO2023201133A1 (en) 2022-04-14 2023-10-19 Board Of Regents Of The University Of Nebraska Cell therapy for alzheimer's disease
US20250297282A1 (en) 2022-05-05 2025-09-25 Juno Therapeutics Gmbh Viral-binding protein and related reagents, articles, and methods of use
WO2023220655A1 (en) 2022-05-11 2023-11-16 Celgene Corporation Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy
EP4279085A1 (en) 2022-05-20 2023-11-22 Mnemo Therapeutics Compositions and methods for treating a refractory or relapsed cancer or a chronic infectious disease
US20250345432A1 (en) 2022-05-25 2025-11-13 Celgene Corporation Method for predicting response to a t cell therapy
WO2023230581A1 (en) 2022-05-25 2023-11-30 Celgene Corporation Methods of manufacturing t cell therapies
WO2023250400A1 (en) 2022-06-22 2023-12-28 Juno Therapeutics, Inc. Treatment methods for second line therapy of cd19-targeted car t cells
AU2023289696A1 (en) 2022-06-24 2025-01-16 Tune Therapeutics, Inc. Compositions, systems, and methods for reducing low-density lipoprotein through targeted gene repression
EP4547230A1 (en) 2022-06-29 2025-05-07 Juno Therapeutics, Inc. Lipid nanoparticles for delivery of nucleic acids
CA3261865A1 (en) 2022-07-12 2024-01-18 Tune Therapeutics, Inc. Compositions, systems, and methods for targeted transcriptional activation
US20260027145A1 (en) 2022-07-27 2026-01-29 Sana Biotechnology, Inc. Methods of transduction using a viral vector and inhibitors of antiviral restriction factors
CA3263560A1 (en) 2022-08-05 2024-02-08 Juno Therapeutics, Inc. Chimeric antigen receptors specific for gprc5d and bcma
KR20250077608A (en) 2022-08-19 2025-05-30 튠 쎄라퓨틱스, 인코포레이티드 Compositions, systems and methods for controlling hepatitis B virus through targeted gene inhibition
CN120435310A (en) 2022-08-26 2025-08-05 朱诺治疗学股份有限公司 Antibodies and chimeric antigen receptors specific for delta-like ligand 3 (DLL3)
CN120152717A (en) 2022-09-08 2025-06-13 朱诺治疗学股份有限公司 Combination of T cell therapy and continuous or intermittent DGK inhibitor administration
WO2024064642A2 (en) 2022-09-19 2024-03-28 Tune Therapeutics, Inc. Compositions, systems, and methods for modulating t cell function
WO2024062138A1 (en) 2022-09-23 2024-03-28 Mnemo Therapeutics Immune cells comprising a modified suv39h1 gene
WO2024097905A1 (en) 2022-11-02 2024-05-10 Celgene Corporation Methods of treatment with t cell therapy and immunomodulatory agent maintenance therapy
EP4615960A1 (en) 2022-11-09 2025-09-17 C3S2 GmbH Methods for manufacturing engineered immune cells
EP4630782A1 (en) 2022-12-09 2025-10-15 Juno Therapeutics, Inc. Machine learning methods for predicting cell phenotype using holographic imaging
KR20250135354A (en) 2022-12-13 2025-09-12 주노 쎄러퓨티크스 인코퍼레이티드 Chimeric antigen receptor specific for BAFF-R and CD19 and methods and uses thereof
WO2024163683A2 (en) 2023-02-01 2024-08-08 Tune Therapeutics, Inc. Systems, compositions, and methods for modulating expression of methyl-cpg binding protein 2 (mecp2) and x-inactive specific transcript (xist)
WO2024163678A2 (en) 2023-02-01 2024-08-08 Tune Therapeutics, Inc. Fusion proteins and systems for targeted activation of frataxin (fxn) and related methods
TW202502363A (en) 2023-02-28 2025-01-16 美商奇諾治療有限公司 Cell therapy for treating systemic autoimmune diseases
KR20250169631A (en) 2023-04-18 2025-12-03 주노 쎄러퓨티크스 인코퍼레이티드 Cytotoxicity assay to evaluate the efficacy of therapeutic cell compositions
WO2024243365A2 (en) 2023-05-23 2024-11-28 Juno Therapeutics, Inc. Activation markers of t cells and method for assessing t cell activation
WO2025029835A1 (en) 2023-07-31 2025-02-06 Tune Therapeutics, Inc. Compositions and methods for modulating il-2 gene expression
WO2025029840A1 (en) 2023-07-31 2025-02-06 Tune Therapeutics, Inc. Compositions and methods for multiplexed activation and repression of t cell gene expression
WO2025038494A1 (en) 2023-08-11 2025-02-20 Tune Therapeutics, Inc. Compositions, systems, and methods for lymphoid cell differentiation using targeted gene activation
WO2025059073A1 (en) 2023-09-11 2025-03-20 Tune Therapeutics, Inc. Epigenetic editing methods and systems for differentiating stem cells
WO2025059362A1 (en) 2023-09-13 2025-03-20 Juno Therapeutics, Inc. Combination therapies with a cell therapy expressing a gprc5d-targeting car and related methods and uses
WO2025076472A1 (en) 2023-10-06 2025-04-10 Juno Therapeutics, Inc. Combination therapies with a cell therapy expressing a gprc5d-targeting car and related methods and uses
WO2025147545A1 (en) 2024-01-03 2025-07-10 Juno Therapeutics, Inc. Lipid nanoparticles for delivery of nucleic acids and related methods and uses
WO2025163107A1 (en) 2024-02-01 2025-08-07 Institut Gustave Roussy Immune cells defective for znf217 and uses thereof
WO2025184421A1 (en) 2024-02-28 2025-09-04 Juno Therapeutics, Inc. Chimeric antigen receptors and antibodies specific for delta-like ligand 3 (dll3) and related methods
WO2026008700A1 (en) 2024-07-03 2026-01-08 Immunofusion Bv Il7r alpha signalling domain, chimeric antigen receptor and uses thereof
WO2026015647A1 (en) 2024-07-09 2026-01-15 Tune Therapeutics, Inc. Compositions, systems, and methods for cell differentiation using targeted gene activation of dll4 and/or vcam1
WO2026020055A2 (en) 2024-07-18 2026-01-22 Juno Therapeutics, Inc. Methods for assessing exosomes in a cell composition and related uses
WO2026025092A1 (en) 2024-07-26 2026-01-29 Juno Therapeutics, Inc. Synthetic promoters for t cell expression

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5436146A (en) * 1989-09-07 1995-07-25 The Trustees Of Princeton University Helper-free stocks of recombinant adeno-associated virus vectors
US5474935A (en) * 1990-05-23 1995-12-12 The United States Of America As Represented By The Department Of Health And Human Services Adeno-associated virus (AAV)-based eucaryotic vectors
US5478745A (en) * 1992-12-04 1995-12-26 University Of Pittsburgh Recombinant viral vector system
US5866696A (en) * 1992-06-02 1999-02-02 The United States Of America As Represented By The Department Of Health And Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
US6033885A (en) * 1994-03-03 2000-03-07 Rhone-Poulenc Rorer S.A. Integrative recombinant adenoviruses, preparation thereof and therapeutical uses thereof
US6207453B1 (en) * 1996-03-06 2001-03-27 Medigene Ag Recombinant AAV vector-based transduction system and use of same
US6342390B1 (en) * 1994-11-23 2002-01-29 The United States Of America As Represented By The Secretary Of Health And Human Services Lipid vesicles containing adeno-associated virus rep protein for transgene integration and gene therapy

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08507921A (en) * 1993-03-19 1996-08-27 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Method for preparing cancer vaccine
US5693531A (en) * 1993-11-24 1997-12-02 The United States Of America As Represented By The Department Of Health And Human Services Vector systems for the generation of adeno-associated virus particles

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5436146A (en) * 1989-09-07 1995-07-25 The Trustees Of Princeton University Helper-free stocks of recombinant adeno-associated virus vectors
US5474935A (en) * 1990-05-23 1995-12-12 The United States Of America As Represented By The Department Of Health And Human Services Adeno-associated virus (AAV)-based eucaryotic vectors
US5866696A (en) * 1992-06-02 1999-02-02 The United States Of America As Represented By The Department Of Health And Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
US5989540A (en) * 1992-06-02 1999-11-23 The United States Of America As Represented By The Department Of Health & Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
US5478745A (en) * 1992-12-04 1995-12-26 University Of Pittsburgh Recombinant viral vector system
US6033885A (en) * 1994-03-03 2000-03-07 Rhone-Poulenc Rorer S.A. Integrative recombinant adenoviruses, preparation thereof and therapeutical uses thereof
US6342390B1 (en) * 1994-11-23 2002-01-29 The United States Of America As Represented By The Secretary Of Health And Human Services Lipid vesicles containing adeno-associated virus rep protein for transgene integration and gene therapy
US6207453B1 (en) * 1996-03-06 2001-03-27 Medigene Ag Recombinant AAV vector-based transduction system and use of same
US6440742B1 (en) * 1996-03-06 2002-08-27 Medigene, Ag Recombinant AAV vector-based transduction system and use of same

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070032570A1 (en) * 2003-11-11 2007-02-08 Canon Kabushiki Kaisha Ink comprising a block copolymer dispersing agent having a hydrophilic and a hydrophobic segment and an ink-applying process and apparatus using the same

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