Adenovirus helper-free system for producing recombinant AAV viri

Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Primate cell – per se

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4353201, 536 231, 536 2372, 536 241, C12N 508

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active

059453354

ABSTRACT:
Composition and methods are provided for producing recombinant AAV ("rAAV") in the absence of helper virus, such as adenovirus. The compositions provide the accessory functions necessary for supporting rAAV virion production in host cells. In certain embodiments, the accessory functions are provided by vectors comprising nucleotide sequences from an adenoviral E4 region which lack the putatively oncogenic E4 ORF 6 coding region. The present invention also includes host cells transfected by the claimed accessory function vectors, methods of using such vectors, and rAAV virions produced by such methods.

REFERENCES:
"Production of High-Titer Recombinant Adeno-Associated Virus Vectors in the Absence of Helper Adenovirus", Xiao et al., Journal of Virology, vol. 72, No. 3, Mar. 1998, pp. 2224-2232.
"Human Adenovirus Early Region 4 Open Reading Frame 1 Genes Encode Growth-Transforming Proteins That May Be Distantly Related to dUTP Pyrophosphatase Enzymes", Weiss et al., Journal of Virology, vol. 71, No. 3, Mar. 1997, pp. 1857-1870.
"Oncogenic Potential of the Adenovirus E4orf6 Protein", Moore et al., Proc. Natl. Acad. Sci., vol. 93, Oct. 1996, pp. 11295-11301.
"Adenovirus Type 9 E4 Open Reading Frame 1 Encodes a Transforming Protein Required for the Production of Mammary Tumors in Rats", Javier, Journal of Virology, vol. 68, No. 6, Jun. 1994, pp. 3917-3924.
"Locations of Adenovirus Genes Required for the Replication of Adenovirus-Associated Virus", Janik et al., Proc. Natl. Acad. Sci., vol. 78, No. 3, Mar. 1981, pp. 1925-1929.

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