RAS antisense inhibition

Details RAS antisense inhibition RAS antisense inhibition

1997-11-07

1999-02-23

LeGuyader, John L.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

435 6, 435 911, 4351723, 435325, 435366, 435375, 536 231, 536 2431, 536 245, A61K 4800, C07H 2104, C12Q 168

Patent

active

058744169

ABSTRACT:
A single stranded oligonucleotide complementary to a specific region of a gene promoter, methylated at carbon 5 of all cytosine residues in cytosine-guanine (CG) dinucleotides, is provided. The modified oligonucleotide provides DNA methyltransferase (MTase) enzyme with a hemimethylated substrate so that DNA MTase can methylate complementary CG sites using methylated oligonucleotides as the template. Such methylation prevents translation of the gene. An oligonucleotide complementary to the sense strand of c-Ha-ras promoter having a methyl group on all cytosine residues of its 6 CpG sites was specifically effective in inhibiting breast tumor cell proliferation and tumorigenicity.

REFERENCES:
Rachal et al. In Vitro DNA Cytosine Methylation of cis-Regulatory Elements Modulates c-Ha-ras Promoter Activity In Vivo. Nucleic Acids Res 17 (13), 5135-5147 (1989).
Bennett et al., Parmacology of Antisense Therapeutic Agents: Cancer and Inflammation, in Antisense Therapeutics, pp. 13-46, (Shudir Agrawal, ed. 1996).
Gewirtz et al., Facilitating oligonucleotide delivery: Helping antisense deleiver on its promise, PNAS 93, 3161-63 (1996).

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