Methods and compositions for the selective inhibition of...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/11 (2006.01) A61K 31/70 (2006.01) A61K 38/17 (2006.01) A61K 48/00 (2006.01) C07H 21/02 (2006.01) C07K 14/82 (2006.01) C12N 15/85 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2108144

2108144 9215680 PCTABS00016 Disclosed are methods and compositions for the selective inhibition gene expression through the application of antisense RNA technology. Antisense RNA constructs of the present invention employ the use of antisense intron DNA corresponding to distinct intron regions of the gene whose expression is targeted for down-regulation. In an exemplary embodiment, a human lung cancer cell line (NCI-H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a genomic segment of K-ras in antisense orientation. Translation of the mutated K-ras mRNA was specifically inhibited, whereas expression of H-ras and N-ras was unchanged. A three-fold growth inhibition occurred in H460a cells when expression of the mutated ras p21 protein was down-regulated by antisense RNA and cells remained viable. The growth of H460a tumors in nu/nu mice was substantially reduced by expressed K-ras antisense RNA.

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