Vector for the expression of two foreign genes

Chemistry: molecular biology and microbiology – Vector – per se

Reexamination Certificate

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C435S091100, C435S091400, C435S091410, C435S091420, C435S455000, C435S456000, C435S457000, C435S235100, C536S023100, C536S023720, C536S024100, C424S093200

Reexamination Certificate

active

06979568

ABSTRACT:
A vector expressing two foreign genes by using RRE sequence and controlling the ratio of the expression doses of these genes owing to the modification is provided. This vector, which can be provided as a lentivirus vector based on SIVagm, is constructed by modifying a virus-origin expression regulatory sequence into another expression regulatory sequence so as to eliminate the dependency on the virus-origin protein. Although this vector has a packaging signal, it has been modified so that the risk of the occurrence of wild strains due to gene recombination is lowered and no virus structural protein is expressed. This vector is highly useful as a gene therapeutic vector with a need for transferring two genes while controlling the expression doses or expression dose ration thereof.

REFERENCES:
patent: 5994136 (1999-11-01), Naldini et al.
patent: WO 97/12622 (1997-04-01), None
patent: WO 99/15683 (1999-04-01), None
patent: WO 99/31251 (1999-06-01), None
patent: WO 00/29421 (2000-05-01), None
patent: WO 00/29557 (2000-05-01), None
Dull et al., “A Third-Generation Lentivirus Vector with a Conditional Packaging System,”J. Virol.,72:8463-8471 (1998).
Zufferey et al., “Self-Inactivating Lentivirus Vector for Safe and Efficient in vivo Gene Delivery,”J. Virol.,72:9873-9880 (1998).
Farson et al., “A New-Generation Stable Inducible Packaging Cell Line for Lentiviral Vectors,”Human Gene Therapy12:981-997 (2001).
Nakajima et al., “Development of Novel Simian Immunodeficiency Virus Vectors Carrying a Dual Gene Expression System,”Human Gene Therapy, 11:1863-1874 (2000).
Rappa et al., “Novel Bicistronic Retroviral Vector Expressing γ-Glutamylcysteine Synthetase and the Multidrug Resistance Protein 1 (MRP1) Protects Cells from MRP1-Effluxed Drugs and Alkylating Agents,”Human Gene Therapy12:1785-1796 (2001).
Barksdale and Baker, “The Human Immunodeficiency Virus Type 1 Rev Protein and the Rev-Responsive Element Counteract the Effect of an Inhibitory 5′ Splice Site in a 3′ Untranslated Region,”Mol. Cell. Biol.,15(6):2962-2971, 1995.
Brighty and Rosenberg, “A Cis-Acting Repressive Sequence that Overlaps the Rev-Responsive Element of Human Immunodeficiency Virus Type 1 Regulates Nuclear Retention ofenvmRNAs Independently of Known Splice Signals,”Proc. Natl. Acad. Sci. USA,91(18):8314-8318, 1994.
Dougherty and Temin, “High Mutation Rate of a Spleen Necrosis Virus-Based Retrovirus Vector,”Mol. Cell. Biol.,168(3):4387-4395, 1986.
Korman et al., “Expression of Human Class II Major Histocompatibility Complex Antigens Using Retrovirus Vectors,”Proc. Natl. Acad. Sci. USA,84(8):2150-2154, 1987.
Naldini et al., “In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector,”Science, 272(5259):263-267, 1996.

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