Alnylam Pharmaceuticals, Inc.

Shigeo Matsuda

Muthiah Manoharan

Kallanthottathil G Rajeev

Martin A Maier

Muthusamy Jayaraman

Akin Akinc

Pachamuthu Kandasamy

Jayaprakash K Nair

Thomas A Baillie

Vasant R Jadhav

Klaus Charisse

Mark K Schlegel

Maja Janas

Alexander V Kelin

Christopher Brown

Stuart Milstein

Alfica Sehgal

Donald Foster

Alexander V Kel'in

Kevin Fitzgerald

Narayanannair K Jayaprakash

Sudhakar Rao Takkellapati

David Butler

Rubina G Parmar

Ivan Zlatev

Guo He

Jayaprakash K Narayanannair

Rajendra K Pandey

Christopher S Theile

Hartmut Ingo Jahns

Pawan Kumar

Masaaki Akabane-nakata

Takeshi Yamada

Chang Geng Peng

Nate Taneja

The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

Biodegradable lipids for the delivery of active 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 relate 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

One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. Other aspects of the invention relate 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.

Compositions and methods for improving strand biased

The present invention relates to ligand conjugates of oligonucleotides (e.g., iRNA agents) and methods for their preparation. The ligands are derived primarily from monosaccharides These conjugates are useful for the in vivo delivery of oligonucleotides.

Oligonucleotide-ligand conjugates and process for their preparation

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

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Cambridge, MA, United States of America

Shigeo Matsuda