Small activating RNA molecules and methods of use
View Patent ↗The present invention provides compositions, pharmaceutical preparations, kits and methods for increasing expression of a gene product in a cell by contacting the cell with a small activating RNA (saRNA) molecule comprising a ribonucleic strand that is complementary to a non-coding nucleic acid sequence of the gene.
1. A method of increasing the expression of a p21 gene comprising:
introducing a double stranded small activating RNA (saRNA) molecule 19-21 base pairs in length into a mammalian cell to increase expression of the p21 gene, wherein the saRNA molecule comprises a first ribonucleic acid strand comprising:
a 5′ region of complementarity to a promoter region of the p21 gene; and
a 3′ terminal region of at least one nucleotide that is non-complementary to the promoter region,
wherein introducing the saRNA molecule increases expression of the p21 gene,
wherein the promoter region is a region comprising a sequence that forms a duplex with a nucleic acid having the sequence of SEQ ID NO: 24,
wherein dTdT sequence in SEQ ID NO: 24 is an overhang that does not form the duplex.
2. The method of claim 1 , wherein the saRNA molecule is introduced into the mammalian cell by expression from a nucleic acid vector.
3. The method of claim 1 , wherein the saRNA molecule comprises a thio modified internucleotide linkage.
4. A method of increasing the expression of a p21 gene comprising:
introducing a 19-21 by long small activating RNA (saRNA) molecule into a mammalian cell to increase expression of the p21 gene,
wherein the saRNA molecule comprises a first ribonucleic acid strand comprising the nucleic acid sequence of SEQ ID NO:23 (5′-CCAACUCAUUCUCCAAGUA[dT][dT]-3′) and a second ribonucleic acid strand comprising the nucleic acid sequence of SEQ ID NO: 24 (5′-UACUUGGAGAAUGAGUUGG[dT][dT]-3′),
wherein introducing the saRNA molecule increases expression of the p21 gene.
5. The method of claim 4 , wherein the saRNA molecule is introduced into the mammalian cell by expression from a nucleic acid vector.
6. The method of claim 4 , wherein the mammalian cell is a cultured cell in vitro.
7. The method of claim 4 , wherein the mammalian cell is in situ in a host.