Title:
IMPROVED NEGATIVE-STRAND RNA VIRAL VECTOR
Document Type and Number:
WIPO Patent Application WO/2016/125364
Kind Code:
A1
Abstract:
The present invention addresses the problem of providing an improved negative-strand RNA viral vector enabling transient high expression of a gene carried by the vector, and quick removal of the vector after the expression, and the use thereof. It was found that if a degron is added to a P-protein possessed by a negative-strand RNA viral vector, high-level expression of a gene carried by the vector is transiently induced after introduction of the vector, and thereafter, the vector can be quickly removed in a manner dependent on the degron. In particular, if the degron is added to a temperature-sensitive P-protein, the vector can be removed to a level below the detection limit within two weeks after cells are infected with the vector. Since the present invention is useful for transiently expressing a transcription factor, such as a reprogramming factor or the like, in target cells, and then quickly removing the vector, the present invention is expected to be applied in cell therapy and regenerative medicine.
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Inventors:
SAEKI KOICHI (JP)
Application Number:
PCT/JP2015/081921
Publication Date:
August 11, 2016
Filing Date:
November 13, 2015
Export Citation:
Assignee:
ID PHARMA CO LTD (JP)
International Classes:
C12N15/09; C12N7/04
Domestic Patent References:
| WO2008133206A1 | 2008-11-06 | |||
| WO2007032555A1 | 2007-03-22 |
Foreign References:
| US20090215169A1 | 2009-08-27 |
Other References:
GARCIN D. ET AL.: "A short peptide at the amino terminus of the Sendai virus C protein acts as an independent element that induces STAT1 instability", J. VIROL., vol. 78, no. 16, 2004, pages 8799 - 8811
BAN H. ET AL.: "Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors", PROC. NATL. ACAD. SCI. USA, vol. 108, no. 34, 2011, pages 14234 - 14239
NISHIMURA K. ET AL.: "Manipulation of KLF4 expression generates iPSCs paused at successive stages of reprogramming", STEM CELL REPORTS, vol. 3, no. 5, 2014, pages 915 - 929
NISHIMURA K. ET AL.: "An auxin-based degron system for the rapid depletion of proteins in nonplant cells", NAT. METHODS, vol. 6, no. 12, 2009, pages 917 - 922
BAN H. ET AL.: "Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors", PROC. NATL. ACAD. SCI. USA, vol. 108, no. 34, 2011, pages 14234 - 14239
NISHIMURA K. ET AL.: "Manipulation of KLF4 expression generates iPSCs paused at successive stages of reprogramming", STEM CELL REPORTS, vol. 3, no. 5, 2014, pages 915 - 929
NISHIMURA K. ET AL.: "An auxin-based degron system for the rapid depletion of proteins in nonplant cells", NAT. METHODS, vol. 6, no. 12, 2009, pages 917 - 922
Attorney, Agent or Firm:
HARUNA, Masao et al. (JP)
Masao Haruna (JP)
Masao Haruna (JP)
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