Chemistry: molecular biology and microbiology – Vector – per se
Patent
1995-05-05
1998-11-17
Guzo, David
Chemistry: molecular biology and microbiology
Vector, per se
536 232, 536 2372, C12N 1586
Patent
active
058375325
ABSTRACT:
A herpes simplex virus type I (HSV-1) mutant capable of establishing latent infection in the absence of in vivo viral replication in neuronal cells and of expressing an inserted therapeutic gene, which comprising: (i) a DNA sequence change in the gene coding for Vmw65 protein, such as to substantially remove the transducing properties while retaining its structural role and thereby preventing in vivo replication, the DNA sequence change being achieved by a transition or transversion alteration of 1 to 72 base pairs, an oligonucleotide insert of 3 to 72 base pairs, or a deletion of 3 to 72 base pairs, at a position between amino acids 289 and 412 of the protein; and (ii) a therapeutic gene inserted into a region of the HSV-1 genome which is non-essential for culture of the virus, and a promoter therefor able to express the therapeutic gene in neuronal cells in vivo. The preferred insertion site for the therapeutic gene (e.g. tyrosine hydroxylase gene) is within the thymidine kinase gene of HSV in 1814.
REFERENCES:
patent: 4859587 (1989-08-01), Roizman
patent: 5501979 (1996-03-01), Geller et al.
A.I. Geller and X.O. Breakefield; A Defective HSV-1 Vector Expresses Escherichia coli .beta.-Galactosidase in Cultured Peripheral neurons; Science (1988).
Breakfield et al., "Herpes Simplex Virus for Gene Delivery to Neurons", The New Biologist, vol. 3, No. 3, 1991, pp. 203-218.
Journal of Virology, vol. 63, No. 5, May 1989, Chris I. Ace et al.: "Construction and Characterization of a Herpes Simplex Virus Type 1 Mutant Unable to Transinduce Immediate-Early Gene Expression", See p. 2260--p. 2269--see the whole document.
Science, vol. 244, Jun. 1989, Theodore Friedmann: "Progress Toward Human Gene Therapy", see p. 1275--p. 1280--p. 1277.
Science, vol. 241, Sep. 1988, Alfred I Geller et al.: "A Defective HSV-1 Vector Express Escherichia coli B-Galactosidasein Cultured Peripheral Neurons", see p. 1667--p. 1669--see whole document.
Ace Christopher Ian
Preston Christopher Maurice
British Technology Group Limited
Guzo David
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