Modified adeno-associated virus vector capable of expression fro

Details Modified adeno-associated virus vector capable of expression fro Modified adeno-associated virus vector capable of expression fro

1992-06-02

1996-12-24

Guzo, David

Chemistry: molecular biology and microbiology

Spore forming or isolating process

4353201, 435 691, 536 231, 536 235, 536 241, C12N 510, C12N 1586, C07H 2104

Patent

active

055873081

ABSTRACT:
Described herein are constructions of recombinant DNA comprising modified adeno-associated virus (AAV) DNA sequences capable of functioning as a eukaryotic expression vector for expressing foreign DNA sequences using a novel transcription promoter comprising the termini of AAV DNA. It is shown that expression of a test reporter gene can be obtained from this vector in mammalian cells. It is further shown that this combination of vector and promoter can be used to introduce and express a human gene and correct a genetic defect in human cells resulting from malfunction of the mutant endogenous gene. Further, the vector can be used to correct the genetic defect by expressing a modified version of the human gene consisting of a fusion of part of the said gene and a synthetic sequence contained in the vector.

REFERENCES:
patent: 4797368 (1989-01-01), Carter et al.
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Wickens et al, "Role of the Conserved AAVAAA Sequence: Four AAVAAA Point Mutants Prevent Messenger RNA 3' End Formation", Science, vol. 226, 1984, pp. 1045-1051.
Srivastava et al. "Construction of a Recombinant Human Parvovirus B319: Adeno-Associated Virus 2 (AAV) DNA Inverted Terminal Repeats are Functional in an AAV-B19 Hybrid Virus", PNAS, vol. 86, pp. 8078-8082, Oct. 1989.
Rosenfeld et al. "In vivo Transfer of the Human Cystic Fibrosis Transmembrane Conductance Regulator Gene to the Airway Epithelium" Cell, vol. 68, pp. 143-155, Jan. 10, 1992.
Beaton et al., "Expression from the Adeno-Associated Virus p5 and p19 Promoters is Negatively Regulated in trans by the rep Protein", Journal of Virology 63:4450-4454 (1989).
Riordan et al., "Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complimentary DNA", Science 245:1066-1073 (1989).
Collins et al., "Cystic Fibrosis: Molecular Biology and Therapeutic Implications" Science 256:774-779 (1992).

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