Alnylam Pharmaceuticals, Inc.

Sirna Therapeutics, Inc.

Other

Vasant R Jadhav

Martin A Maier

Kallanthottathil G Rajeev

Muthiah Manoharan

Stuart Milstein

Rubina G Parmar

Jayaprakash K Nair

Don Foster

Satya Kuchimanchi

Kevin Fitzgerald

Klaus Charisse

Mark K Schlegel

Laura Sepp-Lorenzino

Shigeo Matsuda

Donald Foster

Muthusamy Jayaraman

Adam Castoreno

Ivan Zlatev

Gregory Hinkle

Akin Akinc

Duncan F Brown

James A McSwiggen

Chandra Vargeese

Steven L Colletti

Francis Gosselin

Thomas Joseph Tucker

Anthony W Shaw

Weimin Wang

Aarron T Willingham

Yu Yuan

Alexander V Kel'in

Maja Janas

Tracy Stage Zimmermann

Christopher Brown

Amy Chan

James Butler

Alfica Sehgal

Walter R Strapps

Tayeba Khan

Christopher S Theile

Kirk Brown

Shannon Fishman

Marija Tadin-strapps

David M Tellers

Pachamuthu Kandasamy

Denise M Kenski

Brian Allen Carr

Svetlana Shulga Morskaya

James Mcswiggen

Shawn Patrick Zinnen

Guo He

John M Maraganore

Narendra Vaish

David Morrissey

Mark Keating

Huilei Xu

Stanley F Barnett

Daniel Zewge

Jeffrey G Aaronson

Pushkal Garg

Mangala Meenakshi Soundarapandian

Narendra K Vaish

Susan Radka

Hartmut Ingo Jahns

Jae Kim

Patrick Haslett

Aaron A Momose

Zinnen Shawn

Nate Taneja

Shawn Zinnen

Laura Sepp-lorenzino

Svetlana Shulga-Morskaya

Rene Bartz

The invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs at one or more internal positions on at least one strand, optionally via a linker or carrier.

Extrahepatic delivery

One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2'-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

Modified 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 sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises.at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2'-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

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

The present invention relates, in general to agents that modulate the pharmacological activity of conjugated siRNAs.

REVERSIR™ compounds

The present invention relates, in general to, compounds, compositions and methods useful for modulating gene expression of multiple target nucleic acids by a single chemical entity.

Multi-targeted single entity conjugates

The present disclosure relates to double stranded RNA agents targeting the hepatitis B virus (HBV) genome, and methods of using such agents to inhibit expression of one or more HBV genes and methods of treating subjects having an HBV infection or HBV-associated disorder, e.g., chronic hepatitis B infection.

Hepatitis B virus (HBV) dsRNA agent compositions and methods of use thereof

The present invention provides iRNA agents, e.g., double stranded iRNA agents, that target the transthyretin (TTR) gene and methods of using such iRNA agents for treating or preventing TTR-associated diseases.

Transthyretin (TTR) iRNA compositions and methods of use thereof for treating or preventing TTR-associated diseases

The present invention relates, in general to agents that modulate the pharmacological activity of siRNAs. In addition, the invention relates generally to methods and systems for use in assessing the efficacy and safety of a pharmaceutical composition for use in the treatment or prophylaxis of a disease.

Tunable Reversir™ compounds

One aspect of the present invention relates to a double stranded iRNA agent comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; and one or more lipophilic moieties conjugated to one or more internal positions on at least one strand, optionally via a linker or carrier. Another aspect of the invention relates to a method of gene silencing, comprising administering to a cell or a subject in need thereof a therapeutically effective amount of the lipophilic moieties-conjugated double-stranded iRNAs.

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 invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the TMPRSS6 gene, and methods of using such RNAi agents to inhibit expression of TMPRSS6 and methods of treating subjects having a TMPRSS6 associated disorder, e.g., an iron overload associated disorder, such as &#x3b2;-thalassemia or hemochromatosis.

TMPRSS6 iRNA compositions and methods of use thereof

Growing community of inventors

Sharon, MA, United States of America

Vasant R Jadhav