Modified Small Activating RNA Molecules and Methods of Use

摘要

Methods, compositions and kits are provided for increasing the expression of a gene product in a cell by contacting the cell with a modified small activating RNA (saRNA) molecule, which provides for an increase in gene expression that is improved over the increase in expression provided by traditional saRNAs. These methods and compositions find use in any application in which an increase in gene expression in a cell is desired.

主权项

1. A method for increasing the expression of a p21 gene in a cell, the method comprising:
introducing into a cell an effective amount of a modified p21 gene-specific small activating RNA (saRNA), the modified p21 gene-specific saRNA comprising:
i. an antisense strand comprising a mismatch at the 5′terminal nucleotide compared to antisense strand of a p21 gene-specific control saRNA; andii. a sense strand of the p21 gene-specific control saRNA, the sense strand comprising a blocking moiety at the 5′ terminus; wherein the expression of the p21 gene is increased, wherein the increase in expression of the p21 gene by introduction of said modified gene-specific saRNA is greater than the increase in expression of a gene following administration of said p21 gene-specific control saRNA, and the off-target effects of the modified p21 gene-specific saRNA are less than the off-target effects following introduction of said p21 gene-specific control saRNA, wherein the sense and antisense strands form a duplex region of between 15 to 30 base pairs in the modified saRNA molecule.