WO1996037623B1 - Retroviral vectors - Google Patents
Retroviral vectorsInfo
- Publication number
- WO1996037623B1 WO1996037623B1 PCT/GB1996/001230 GB9601230W WO9637623B1 WO 1996037623 B1 WO1996037623 B1 WO 1996037623B1 GB 9601230 W GB9601230 W GB 9601230W WO 9637623 B1 WO9637623 B1 WO 9637623B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- retroviral vector
- promoter
- gene
- retrovirus
- genes
- Prior art date
Links
- 230000001177 retroviral Effects 0.000 title claims abstract 15
- 229920003013 deoxyribonucleic acid Polymers 0.000 claims abstract 11
- 230000001105 regulatory Effects 0.000 claims abstract 10
- 241001430294 unidentified retrovirus Species 0.000 claims abstract 8
- 229920000160 (ribonucleotides)n+m Polymers 0.000 claims abstract 4
- 230000001939 inductive effect Effects 0.000 claims abstract 3
- 238000001415 gene therapy Methods 0.000 claims abstract 2
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 claims abstract 2
- 230000001225 therapeutic Effects 0.000 claims 3
- 241000714177 Murine leukemia virus Species 0.000 claims 1
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims 1
- 201000009910 diseases by infectious agent Diseases 0.000 claims 1
- 102000034448 gene-regulatory proteins Human genes 0.000 claims 1
- 108091006088 gene-regulatory proteins Proteins 0.000 claims 1
- 238000003780 insertion Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 238000004806 packaging method and process Methods 0.000 claims 1
- 230000035897 transcription Effects 0.000 claims 1
- 230000026683 transduction Effects 0.000 claims 1
- 238000010361 transduction Methods 0.000 claims 1
- 102000007622 Human Immunodeficiency Virus rev Gene Products Human genes 0.000 abstract 1
- 108010071893 Human Immunodeficiency Virus rev Gene Products Proteins 0.000 abstract 1
Abstract
Retroviral vectors are disclosed which are useful in gene therapy. The packageable RNA genome of the vector provides in the DNA provirus a regulated promoter which is inducible by a regulatory factor e.g. the HIV transactivator protein Tat, and at least one selected gene under its transcriptional control. In the DNA provirus, the regulated promoter is present in the 5' long terminal repeat (LTR) in place of the 5'LTR promoter function of the retrovirus, and the selected gene is located between the LTRs. Thus when inserted into a host cell the gene will be expressed only when the DNA provirus is exposed to the regulatory factor.
Claims
1. A retroviral vector based on a first retrovirus, said vector comprising a packagable RNA genome capable of being inserted into a host cell genome when in the form of a DNA provirus, said RNA genome comprising sequences which provide in the DNA provirus: a) a regulated promoter which is inducible by a regulatory factor; b) a selected gene or genes under transcriptional control of the promoter in a); wherein the regulated promoter a) is present in the 5' long terminal repeat (LTR) of the provirus in place of the 5' LTR promoter function of U3 and R of the first retrovirus, and the selected gene or genes b) is located between the LTRs.
2. A retroviral vector as claimed in claim 1 , wherein the regulated promoter a) is inducible by a regulatory protein from a second retrovirus.
3. A retroviral vector as claimed in claim 1 or claim 2, wherein the selected gene is a first therapeutic gene.
4. A retroviral vector as claimed in claim 2 or claim 3, wherein the regulated promoter comprises the U3 and R, or functional portions thereof, of the second retrovirus.
5. A retroviral vector as claimed in any one of claims 1 to 4, wherein the first retrovirus is MLV.
6. A retroviral vector as claimed in any one of claims 2 to 5, wherein the second retrovirus is HIV.
7. A retroviral vector as claimed in any one of claims 1 to 6, further comprising an expression cassette of a constitutive promoter and a second therapeutic gene or a selectable marker gene.
8. A retroviral vector as claimed in any one of claims 1 to 7, comprising a plurality of therapeutic genes present on the same or different transcription units.
9. A retroviral vector as claimed in any one of claims 1 to 8, wherein in the absence of the regulatory factor there is low basal expression of the selected gene or genes from the DNA provirus.
10. A DNA construct encoding the packagable RNA genome for the retroviral vector as claimed in any one of claims 1 to 9, under the control of a promoter.
11. A DNA construct as claimed in claim 10, wherein the promoter originates from a source other than the first or second retrovirus.
12. A DNA construct as claimed in claim 10 or claim 11 , wherein the promoter is the CMV promoter.
13. A DNA construct as claimed in any one of claims 10 to 12, wherein the selected gene is absent and the construct has an insertion site at which the selected or gene or genes may be inserted.
14. A retroviral vector production system comprising a packaging cell line transfected with a DNA construct as claimed in any one of claims 10 to 13, said system capable of producing retroviral vectors as claimed in any one of claims 1 to 9.
15. The use of a retroviral vector as claimed in any one of claims 2 to 9 for gene therapy for infection or transduction of a target cell.
16. Target cells resulting from the method according to claim 15.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT96914342T ATE213780T1 (en) | 1995-05-22 | 1996-05-22 | RETROVIRAL VECTORS |
| EP96914342A EP0827545B1 (en) | 1995-05-22 | 1996-05-22 | Retroviral vectors |
| DE69619514T DE69619514T2 (en) | 1995-05-22 | 1996-05-22 | RETROVIRAL VECTORS |
| DK96914342T DK0827545T3 (en) | 1995-05-22 | 1996-05-22 | Retroviral vectors |
| US08/952,948 US6096538A (en) | 1995-05-22 | 1996-05-22 | Retroviral vectors |
| JP53549496A JP3886531B2 (en) | 1995-05-22 | 1996-05-22 | Retro virus vector |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9510272.9A GB9510272D0 (en) | 1995-05-22 | 1995-05-22 | Retroviral vectors |
| GB9510272.9 | 1995-05-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1996037623A1 WO1996037623A1 (en) | 1996-11-28 |
| WO1996037623B1 true WO1996037623B1 (en) | 1997-01-30 |
Family
ID=10774804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1996/001230 WO1996037623A1 (en) | 1995-05-22 | 1996-05-22 | Retroviral vectors |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6096538A (en) |
| EP (2) | EP0827545B1 (en) |
| JP (1) | JP3886531B2 (en) |
| AT (2) | ATE340864T1 (en) |
| DE (2) | DE69619514T2 (en) |
| DK (1) | DK0827545T3 (en) |
| ES (1) | ES2170856T3 (en) |
| GB (1) | GB9510272D0 (en) |
| PT (1) | PT827545E (en) |
| WO (1) | WO1996037623A1 (en) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE200517T1 (en) | 1994-09-02 | 2001-04-15 | Gsf Forschungszentrum Umwelt | NON-SELF-INACTIVATE RETROVIRAL VECTORS WITH TARGETED EXPRESSION |
| DK0817858T3 (en) | 1995-03-09 | 2003-08-11 | Gsf Forschungszentrum Umwelt | Vectors containing therapeutic genes for antimicrobial peptides for use in gene therapy |
| AU721326B2 (en) * | 1996-02-13 | 2000-06-29 | Fred Hutchinson Cancer Research Center | 10A1 retroviral packaging cells and uses thereof |
| US6776986B1 (en) | 1996-06-06 | 2004-08-17 | Novartis Ag | Inhibition of HIV-1 replication by antisense RNA expression |
| GB9621680D0 (en) | 1996-10-17 | 1996-12-11 | Oxford Biomedica Ltd | Lentiviral vectors |
| GB9622500D0 (en) | 1996-10-29 | 1997-01-08 | Oxford Biomedica Ltd | Therapeutic gene |
| US6924123B2 (en) | 1996-10-29 | 2005-08-02 | Oxford Biomedica (Uk) Limited | Lentiviral LTR-deleted vector |
| GB9703802D0 (en) | 1997-02-24 | 1997-04-16 | Kingsman Susan M | Anti-hiv peptides and proteins |
| GB9711578D0 (en) * | 1997-06-04 | 1997-07-30 | Oxford Biomedica Ltd | Novel retroviral vector production systems |
| DE69830663T2 (en) | 1997-09-24 | 2006-05-11 | The Regents Of The University Of California, Oakland | Non-primate lentivirus vectors and packaging systems |
| US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
| US6790657B1 (en) | 1999-01-07 | 2004-09-14 | The United States Of America As Represented By The Department Of Health And Human Services | Lentivirus vector system |
| ATE456677T1 (en) * | 1999-07-09 | 2010-02-15 | Gen Probe Inc | HIV-1 DETECTION USING NUCLEIC ACID AMPLIFICATION |
| CN1423698A (en) | 1999-11-16 | 2003-06-11 | 真那特应用生物科技有限公司 | The Genome of the HIV-1 inter-subtype (C/B') and use thereof |
| US7575924B2 (en) | 2000-11-13 | 2009-08-18 | Research Development Foundation | Methods and compositions relating to improved lentiviral vectors and their applications |
| WO2002087341A1 (en) * | 2001-05-01 | 2002-11-07 | Genetix Pharmaceuticals, Inc. | Novel self-inactivating (sin) lentiviral vectors |
| ATE527347T1 (en) * | 2001-08-02 | 2011-10-15 | Inst Clayton De La Rech | METHODS AND COMPOSITIONS RELATED TO IMPROVED LENTIVIRUS VECTOR PRODUCTION SYSTEMS |
| ES2601141T3 (en) * | 2001-09-13 | 2017-02-14 | California Institute Of Technology | Method for the expression of small RNA molecules within a cell |
| US7195916B2 (en) * | 2001-09-13 | 2007-03-27 | California Institute Of Technology | Method for expression of small antiviral RNA molecules within a cell |
| US7737124B2 (en) | 2001-09-13 | 2010-06-15 | California Institute Of Technology | Method for expression of small antiviral RNA molecules with reduced cytotoxicity within a cell |
| KR20040054699A (en) * | 2001-10-02 | 2004-06-25 | 엥스띠뛰 끌레이톤 드 라 러쉐르쉬 | Methods and compositions relating to restricted expression lentiviral vectors and their applications |
| JP4598398B2 (en) | 2002-02-01 | 2010-12-15 | オックスフォード バイオメディカ （ユーケー） リミテッド | Virus vector |
| US9738907B2 (en) * | 2002-02-01 | 2017-08-22 | Oxford Biomedica (Uk) Limited | Viral vector |
| US7135324B2 (en) | 2002-09-04 | 2006-11-14 | The University Of Connecticut | Viral recombinases, related articles, and methods of use thereof |
| CN1759182A (en) * | 2002-11-22 | 2006-04-12 | 克雷顿研究院 | Compositions and systems for the regulation of genes |
| US7297536B2 (en) * | 2003-01-23 | 2007-11-20 | Wisconsin Alumni Research Foundation | Inducible protein expression system |
| ES2221578B1 (en) * | 2003-06-13 | 2006-03-01 | Universidad De Jaen | VECTOR DESIGNED FOR THE DESTRUCTION OF LATENT VIRUSES IN THE TREATMENT OF INFECTION BY THE VIRUS OF HUMAN IMMUNODEFICIENCY TYPE 1 (HIV-1) BY GENE THERAPY. |
| GB201318804D0 (en) | 2013-10-24 | 2013-12-11 | Adaptimmune Ltd | Vectors for transgene expression |
| GB201322798D0 (en) | 2013-12-20 | 2014-02-05 | Oxford Biomedica Ltd | Production system |
| US11446398B2 (en) | 2016-04-11 | 2022-09-20 | Obsidian Therapeutics, Inc. | Regulated biocircuit systems |
| JP7097465B2 (en) | 2018-06-19 | 2022-07-07 | アルモ・バイオサイエンシーズ・インコーポレイテッド | Composition of IL-10 agent to be used in combination with chimeric antigen receptor cell therapy and its usage |
| CN114667161A (en) | 2019-11-12 | 2022-06-24 | 牛津生物医学（英国）有限公司 | Production system |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4738922A (en) * | 1984-05-25 | 1988-04-19 | Dana Farber Cancer Institute | Trans-acting transcriptional factors |
| US5591624A (en) * | 1988-03-21 | 1997-01-07 | Chiron Viagene, Inc. | Retroviral packaging cell lines |
| US5665577A (en) * | 1989-02-06 | 1997-09-09 | Dana-Farber Cancer Institute | Vectors containing HIV packaging sequences, packaging defective HIV vectors, and uses thereof |
| US5672510A (en) * | 1990-01-19 | 1997-09-30 | Genetic Therapy, Inc. | Retroviral vectors |
| ES2187504T3 (en) * | 1992-02-28 | 2003-06-16 | Syngenix Ltd | NON-ONCOVIRAL VECTORS, BASED ON THE VMMP, WITH DEFECTIVE ENCAPSIDATION. |
| GB9305759D0 (en) * | 1993-03-19 | 1993-05-05 | Medical Research Council And T | Hiv therapy method and agents |
| WO1994029437A1 (en) * | 1993-06-07 | 1994-12-22 | University Of Medicine & Dentistry Of New Jersey | Highly-efficient, self-inactivating, recombination-free, u3-free retroviral vectors |
| EP0759471A4 (en) * | 1994-05-10 | 1997-10-15 | Hisamitsu Pharmaceutical Co | Recombinant human immunodeficiency virus vector and process for producing the same |
| US5693508A (en) * | 1994-11-08 | 1997-12-02 | Chang; Lung-Ji | Retroviral expression vectors containing MoMLV/CMV-IE/HIV-TAR chimeric long terminal repeats |
-
1995
- 1995-05-22 GB GBGB9510272.9A patent/GB9510272D0/en active Pending
-
1996
- 1996-05-22 ES ES96914342T patent/ES2170856T3/en not_active Expired - Lifetime
- 1996-05-22 DE DE69619514T patent/DE69619514T2/en not_active Expired - Fee Related
- 1996-05-22 WO PCT/GB1996/001230 patent/WO1996037623A1/en active IP Right Grant
- 1996-05-22 DE DE69636581T patent/DE69636581T2/en not_active Expired - Fee Related
- 1996-05-22 US US08/952,948 patent/US6096538A/en not_active Expired - Fee Related
- 1996-05-22 PT PT96914342T patent/PT827545E/en unknown
- 1996-05-22 AT AT01119879T patent/ATE340864T1/en not_active IP Right Cessation
- 1996-05-22 JP JP53549496A patent/JP3886531B2/en not_active Expired - Fee Related
- 1996-05-22 AT AT96914342T patent/ATE213780T1/en not_active IP Right Cessation
- 1996-05-22 EP EP96914342A patent/EP0827545B1/en not_active Expired - Lifetime
- 1996-05-22 DK DK96914342T patent/DK0827545T3/en active
- 1996-05-22 EP EP01119879A patent/EP1164196B1/en not_active Expired - Lifetime
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO1996037623B1 (en) | Retroviral vectors | |
| GB9510272D0 (en) | Retroviral vectors | |
| Zaiss et al. | RNA 3′ readthrough of oncoretrovirus and lentivirus: implications for vector safety and efficacy | |
| AU4712397A (en) | Lentiviral vectors | |
| WO1995007995A3 (en) | Adeno-associated viral (aav) liposomes and methods related thereto | |
| EP0702716A4 (en) | Ribozyme gene therapy for hiv infection and aids | |
| EP0914457A1 (en) | Methods and compositions for transforming cells | |
| ATE291632T1 (en) | LENTIVIRUS-BASED GENE TRANSFER VECTORS | |
| EP0331939A3 (en) | Method and compositions for conferring resistance to retroviral infection | |
| CN1981047A (en) | Methods for dynamic vector assembly of DNA cloning vector plasmids | |
| CA1341119C (en) | Human erythroid-specific transcriptional enhancer | |
| US5556954A (en) | Hematopoietic stem cell specific gene expression | |
| CA2435956A1 (en) | Method for the selection of recombinant clones comprising a sequence encoding an antidote protein to toxic molecule | |
| EP1484409A3 (en) | Expression vector comprising short-lived drug resistance gene | |
| US6534314B1 (en) | Methods and compositions for transforming cells | |
| Ismail et al. | Split-intron retroviral vectors: enhanced expression with improved safety | |
| US20020042136A1 (en) | Retroviral vectors comprising an enhanced 3' transcription termination structure | |
| AU4712497A (en) | Retroviral vectors | |
| AU2419599A (en) | Reconstituting retroviral vector (recon vector) for targeted gene expression | |
| RU99109988A (en) | LENTIVIRUS VECTORS | |
| Kim et al. | Tetracycline-mediated suppression of gene expression with a new dicistronic retroviral vector | |
| Lin et al. | Retrovirus-Mediated Gene Transduction of SupT1 Cells |