Alnylam Pharmaceuticals, Inc.

Arrowhead Pharmaceuticals, Inc.

Novartis Ag

Regeneron Pharmaceuticals, Inc.

Arrowhead Research Corporation

Genzyme Corporation

Stuart Milstein

Martin A Maier

Gregory Hinkle

Kevin Fitzgerald

Brian R Bettencourt

Kallanthottathil G Rajeev

Muthiah Manoharan

Satyanarayana Kuchimanchi

Vasant R Jadhav

William Querbes

Klaus Charisse

Maria Frank-Kamenetsky

Svetlana Shulga Morskaya

Rubina G Parmar

Donald Foster

Don Foster

Antonin De Fougerolles

John Louis Diener

Emma Hickman

Anne-Marie Pulichino

Andrew Griffin Sprague

Satya Kuchimanchi

Ivanka Toudjarska

Markus Warmuth

Tracy Stage Zimmermann

Ping Zhu

Wenlai Zhou

James Butler

Jayaprakash K Nair

Mark K Schlegel

Alfica Sehgal

Muthusamy Jayaraman

Akin Akinc

Dinah Wen-Yee Sah

Qingmin Chen

Alexander V Kel'in

Rene Alvarez

Adam Castoreno

Jan Weiler

Stephanie Williams

John M Maraganore

Abigail Liebow

Shigeo Matsuda

Anna Borodovsky

Laura Sepp-Lorenzino

Dieter Huesken

Maja Janas

Christopher S Theile

Christopher Brown

Emily Thomas

Jennifer Tullai

Kirk Brown

Shanthi Ganesh

Elizabeth George

Shannon Fishman

Jonathan Solomon

Jesper Gromada

Aris I Baras

Xiping Cheng

Frederick E Dewey

Noura S Abul-Husn

Yurong Xin

Omri Gottesman

Frederic Tremblay

Alexander Li

Tuyen Nguyen

Brian Bettencourt

David A Bumcrot

Tatiana Novobrantseva

James D McIninch

Charalambos Kaittanis

Alan R Shuldiner

Mark Keating

Huilei Xu

Frank Peter Stegmeier

Jinyun Chen

Michael Ray Schlabach, Jr

Mangala Meenakshi Soundarapandian

Kalyani Gampa

Mark Stump

Dieter Heusken

Muthiah Monaharan

Jason Gilbert

Alan Shuldiner

Patrick Haslett

Laura Sepp-lorenzino

Michael Jr Schlabach

Earl Mcdonald

Zainab Jagani

Rajeev G Kallanthottathil

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.

Angiopoietin-like 3 (ANGPTL3) iRNA compositions and methods of use thereof

The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the PCSK9 gene, and methods of using such RNAi agents to inhibit expression of PCSK9 and methods of treating subjects having a lipid disorder, such as a hyperlipidemia.

PCSK9 iRNA compositions and methods of use thereof

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.

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the HSD17B 13 gene, as well as methods of inhibiting expression of HSD17B13, and methods of treating subjects that would benefit from reduction in expression of HSD17B13, such as subjects having a HSD17B13-associated disease, disorder, or condition, using such dsRNA compositions.

17ß-hydroxysteroid dehydrogenase type 13 (HSD17B13) iRNA compositions and methods of use thereof

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a transthyretin (TTR) gene, and methods of using the dsRNA to inhibit expression of TTR.

Compositions and methods for inhibiting expression of transthyretin

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 disclosure relates to methods of treating heat shock factor 1 (HSF1)-related diseases such as cancer and viral diseases, using a therapeutically effective amount of a RNAi agent to HSF.

Organic compositions to treat HSF1-related diseases

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.

Growing community of inventors

Cambridge, MA, United States of America

Stuart Milstein