WO1997015679B1 - Recombinant viruses containing mobile genetic elements and methods of use in gene therapy - Google Patents
Recombinant viruses containing mobile genetic elements and methods of use in gene therapyInfo
- Publication number
- WO1997015679B1 WO1997015679B1 PCT/US1996/017176 US9617176W WO9715679B1 WO 1997015679 B1 WO1997015679 B1 WO 1997015679B1 US 9617176 W US9617176 W US 9617176W WO 9715679 B1 WO9715679 B1 WO 9715679B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- gene
- original
- virus
- cell
- expression
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract 14
- 241000700605 Viruses Species 0.000 title claims 12
- 238000001415 gene therapy Methods 0.000 title 1
- 230000002068 genetic effect Effects 0.000 title 1
- 241000701161 unidentified adenovirus Species 0.000 claims abstract 8
- 210000003483 chromatin Anatomy 0.000 claims abstract 6
- 108090000623 proteins and genes Proteins 0.000 claims 13
- 210000004027 cell Anatomy 0.000 claims 12
- 230000001105 regulatory effect Effects 0.000 claims 8
- 241001068295 Replication defective viruses Species 0.000 claims 5
- 108010020764 Transposases Proteins 0.000 claims 4
- 230000037430 deletion Effects 0.000 claims 4
- 238000012217 deletion Methods 0.000 claims 4
- 108091081062 Repeated sequence (DNA) Proteins 0.000 claims 3
- 230000011278 mitosis Effects 0.000 claims 3
- 241001430294 unidentified retrovirus Species 0.000 claims 3
- 108010077544 Chromatin Proteins 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 230000001939 inductive effect Effects 0.000 claims 2
- 230000000394 mitotic effect Effects 0.000 claims 2
- 238000004806 packaging method and process Methods 0.000 claims 2
- 108010057856 Adenovirus E2 Proteins Proteins 0.000 claims 1
- 101150005585 E3 gene Proteins 0.000 claims 1
- 102000008579 Transposases Human genes 0.000 claims 1
- 210000004962 mammalian cell Anatomy 0.000 claims 1
- 230000035772 mutation Effects 0.000 claims 1
- 241000713869 Moloney murine leukemia virus Species 0.000 abstract 2
- 108700019146 Transgenes Proteins 0.000 abstract 2
- 230000018412 transposition, RNA-mediated Effects 0.000 abstract 1
Abstract
Recombinant E1-deleted adenoviruses are provided that contain a transgene associated with the elements of a recombinant transposon sequence, e.g., from Moloney murine leukemia virus (Mo-MLV), necessary to achieve specific retrotransposition of the transgene from the recombinant adenovirus into the target cell chromatin. Also provided are methods for generating the recombinant adenoviruses and methods of use thereof.
Claims
1. A method for delivering and stably integrating a gene into host cell chromatin comprising the steps of:
(a) infecting a host cell with an effective amount of a recombinant replication defective virus comprising:
(i) a first expression sequence comprising a suitable human gene operatively linked regulatory sequences directing its expression; and
(ii) cis-acting terminal repeat sequences of a transposon, wherein the cis-acting sequences flank the gene and regulatory sequences; and
(b) providing the host cell with a transposase.
2. The method according to claim 1, wherein the providing step comprises co-infecting said cell with a second recombinant replication defective virus comprising a second expression sequence comprising a suitable trans¬ acting transposase gene operatively linked to regulatory sequences directing its expression.
3. The method according to claim 2, wherein the second virus is an adenovirus.
4. The method according to any of claims 1-3 wherein said cell is in mitosis.
5. The method according to any of claims 1-3, further comprising the step of inducing a mitotic state in said cell.
6. A recombinant replication defective virus comprising:
(a) a first expression sequence comprising a suitable human gene operatively linked to regulatory sequences directing its expression;
(b) cis-acting terminal repeat sequences of a transposon, wherein the cis-acting sequences flank the gene and regulatory sequences; and
(c) a second expression sequence comprising a suitable trans-acting transposase gene operatively linked to regulatory sequences directing its expression.
7. The virus according to claim 6, which is an adenovirus.
8. The virus according to claim 7, wherein said adenovirus has a deletion in all or a part of the El gene.
9. The virus according to claim 7 or 8 , wherein said adenovirus has a deletion in all or a part of the E3 gene.
10. The virus according to any of claims 7-9, wherein said adenovirus has a temperature sensitive mutation in the adenovirus E2a gene.
11. The virus according -to any of claims 6-10, wherein the first expression sequence is located at the site of any deletion in the virus sequence.
12. The virus according to any of claims 6-10, wherein the second expression sequence includes a sequence and a heterologous promoter.
13. The virus according to any of claims 6-10, wherein the second expression sequence is located at the site of any deletion in the virus sequence.
14. Use of a virus according to any of claims 6-13 in the preparation of a medicament for delivering and stably integrating a gene into host cell chromatin.
15. Use according to claim 14, characterized in that the medicament is administered when the cell is in mitosis.
16. A method for delivering and stably integrating a gene into host cell chromatin comprising the step of infecting the cell with an effective amount of a recombinant replication defective virus according to any of claims 6-13.
17. The method according to claim 16, wherein the cell is in mitosis.
18. The method according to claim 16, further comprising the step of inducing a mitotic state in the cell.
19. A mammalian cell which stably expresses a human gene integrated into its chromatin, produced by the method of any of claims 1-5 or 16-18.
20. A method of generating recombinant retroviruses comprising the step of: infecting a retrovirus packaging cell line containing a transposase gene with a recombinant replication defective virus comprising: (a) a first expression sequence comprising a suitable human gene operatively linked to regulatory sequences directing its expression; and
(b) cis-acting terminal repeat sequences of a transposon, wherein the cis-acting sequences flank the gene and regulatory sequences, wherein the gene is transferred to the chromatin of said cell and the packaging cell line produces recombinant retrovirus containing the human gene.
STATEMENT UNDER ARTICLE 19
Kindly substitute the enclosed claim sheets 27 - 30 for original claim sheets 27 - 31. The claims have been amended as follows.
Claims 1-3 are supported by and correspond to original claims 15-17. Claims 4 and 5 correspond to original claims 19 and 20. Claim 6 has been amended to recite a second expression sequence. This amendment is supported by original claims 1 and 3. Claim 7 corresponds to original claim 2. The dependency of claims 8-13 (formerly claims 4-9) have been amended. Claim 14 (original claim 13) and claim 16 (original claim 15) have been amended to reflect the amendments made to claims 6-13. Claim 15 corresponds to original claim 14. Claim 16 is supported by original claims 1, 3 and 15. Claims 17 and 18 correspond to original claims 19 and 20.
Claim 19 corresponds to original claim 21, but has been amended to recite the methods of claims 1-5 or 16-18. Claim 20 is supported by original claims 15 and 22.
Original claims 3, 10-12, and 18 have been cancelled.
These amendments are further supported throughout the specification. No new matter has been added.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU76653/96A AU7665396A (en) | 1995-10-27 | 1996-10-24 | Recombinant viruses containing mobile genetic elements and methods of use in gene therapy |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US594295P | 1995-10-27 | 1995-10-27 | |
| US60/005,942 | 1995-10-27 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1997015679A1 WO1997015679A1 (en) | 1997-05-01 |
| WO1997015679B1 true WO1997015679B1 (en) | 1997-07-17 |
| WO1997015679A9 WO1997015679A9 (en) | 1997-08-14 |
Family
ID=21718478
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1996/017176 WO1997015679A1 (en) | 1995-10-27 | 1996-10-24 | Recombinant viruses containing mobile genetic elements and methods of use in gene therapy |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU7665396A (en) |
| WO (1) | WO1997015679A1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000076157A (en) | 1997-03-11 | 2000-12-26 | 리전츠 오브 더 유니버스티 오브 미네소타 | Dna-based transposon system for the introduction of nucleic acid into dna of a cell |
| US7160682B2 (en) | 1998-11-13 | 2007-01-09 | Regents Of The University Of Minnesota | Nucleic acid transfer vector for the introduction of nucleic acid into the DNA of a cell |
| US6576463B1 (en) * | 1999-01-15 | 2003-06-10 | The Regents Of The University Of California | Hybrid vectors for gene therapy |
| DE19909156A1 (en) | 1999-03-02 | 2000-09-07 | Aventis Res & Tech Gmbh & Co | Test system for the detection of a splice reaction and its use |
| WO2000068399A2 (en) * | 1999-05-11 | 2000-11-16 | Regents Of The University Of Minnesota | Vector-mediated delivery of integrating transposon sequences |
| WO2001044280A2 (en) * | 1999-12-14 | 2001-06-21 | Genovo, Inc. | Methods and compositions for the manufacture of replication incompetent adenovirus |
| WO2002092786A2 (en) * | 2001-03-26 | 2002-11-21 | The Board Of Trustees Of The Leland Stanford Junior University | A helper dependent adenoviral vector system and methods for using the same |
| WO2003089618A2 (en) | 2002-04-22 | 2003-10-30 | Regents Of The University Of Minnesota | Transposon system and methods of use |
| US7291604B2 (en) | 2003-09-03 | 2007-11-06 | The General Hospital Corporation | Methods of treating restenosis |
| CN101437833A (en) | 2006-02-10 | 2009-05-20 | 辛辛那提大学 | Phosphatase inhibitor protein-1 as a regulator of cardiac function |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU651311B2 (en) * | 1988-03-21 | 1994-07-21 | Chiron Corporation | Recombinant retroviruses |
| US6686200B1 (en) * | 1993-08-31 | 2004-02-03 | Uab Research Foundation | Methods and compositions for the large scale production of recombinant adeno-associated virus |
| FR2716893B1 (en) * | 1994-03-03 | 1996-04-12 | Rhone Poulenc Rorer Sa | Recombinant viruses, their preparation and their therapeutic use. |
| WO1996009399A2 (en) * | 1994-09-23 | 1996-03-28 | Somatix Therapy Corporation | Chimeric adenovirus for gene delivery |
-
1996
- 1996-10-24 WO PCT/US1996/017176 patent/WO1997015679A1/en active Application Filing
- 1996-10-24 AU AU76653/96A patent/AU7665396A/en not_active Abandoned
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