Sirna and compositions thereof

Abstract

The present invention provides siRNA modification patterns that enhance the activity of inhibiting target mRNA expression, reduce off-target effects, increase the biological stability of the molecule, improve the physical stability of the duplex formed between the antisense and sense strands, and / or lower immunogenicity. The invention further provides siRNAs for inhibiting the expression of the MMP7 gene, comprising a sense strand and an antisense strand. Additionally, the invention provides conjugates comprising an siRNA that inhibits MMP7 gene expression and a pharmaceutically acceptable targeting moiety (e.g., an αvβ6 integrin ligand represented by Formula I). The siRNA duplexes, modified duplexes, and conjugates provided herein exhibit excellent stability, outstanding inhibitory activity against the MMP7 gene, negligible cytotoxicity and immunostimulation, and are capable of significantly reducing MMP7 mRNA and protein levels in both cellular and animal models. These compositions hold significant clinical value for the treatment of diseases or conditions that benefit from reduced MMP7 levels or the suppression of its expression.

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