Antisense oligonucleotide compositions for selectively killing c

Details Antisense oligonucleotide compositions for selectively killing c Antisense oligonucleotide compositions for selectively killing c

1994-01-10

1997-06-24

LeGuyader, John

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

435 6, 435 911, 4351721, 536 231, 536 245, A61K 4800, C12Q 168, C12P 1934

Patent

active

056417543

ABSTRACT:
The present invention relates to methods and compositions for the treatment of cancer using an oligonucleotide and an hydroxyl radical up-regulator. The oligonucleotide is characterized by its ability to down-regulate the path by which the cell repairs oxidative damage to its DNA. Thus, the oligonucleotide renders the tumor cells more susceptible to eradication upon exposure to the hydroxyl radical up-regulator administered substantially concomitantly with or subsequent to administration of the oligonucleotide. This novel treatment, preferentially inhibits the proliferation or kills malignant cells but not normal cells. Preferably, the oligonucleotide is antisense to the gene which encodes protein p53, although other antisense oligonucleotides can also be used. The invention also includes novel conjugates of the oligonucleotide and the hydroxyl up-regulator, as well as new oligonucleotides.

REFERENCES:
Stull et al., Pharm. Res. 12:465 (1995).
Kastan, "Participation of p53 Protein in the Cellular Response to DNA Damage", Cancer Research, Dec. 1, 1991, 51:6304-6311.

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