Alnylam Pharmaceuticals, Inc.

Christopher Brown

Muthiah Manoharan

Martin A Maier

Vasant R Jadhav

Klaus Charisse

Jayaprakash K Nair

Shigeo Matsuda

Mark K Schlegel

Kallanthottathil G Rajeev

Stuart Milstein

Muthusamy Jayaraman

Alfica Sehgal

Donald Foster

Alexander V Kel'in

Maja Janas

Kevin Fitzgerald

Guo He

Christopher S Theile

Nate Taneja

Hartmut Ingo Jahns

The invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the Serpina1 gene, and methods of using such RNAi agents to inhibit expression of Serpina1 and methods of treating subjects having a Serpina1 associated disease, such as a liver disorder.

Serpina1 iRNA compositions and methods of use thereof

The present invention relates to a chirally-modified dsRNA agent capable of inhibiting the expression of a target gene. The sense and antisense strands of chirally-modified dsRNA agent independently or in combination comprises one or more site specific-site specific/position specific, chirally-modified internucleotide linkages.

Chirally-enriched double-stranded RNA agents

One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2'-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.

Modified RNA agents with reduced off-target effect

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Cambridge, MA, United States of America

Christopher Brown