Sirna Therapeutics, Inc.

Merck Sharp + Dohme Corp.

Modernatx, Inc.

Merck + Co., Inc.

Sima Therapeutics, Inc.

Sirna Therepeutics, Inc.

Matthew G Stanton

Steven L Colletti

Brian W Budzik

Thomas Allen Miller

David L Sloman

Steven M Stirdivant

James J Cunningham

David James Witter

Gabor Butora

Gregory L Beutner

Jennifer R Davis

Solomon D Kattar

Weimin Wang

Edward John Miracco

Darla Danile Seifried

Kevin J Wilson

Duncan F Brown

Walter R Strapps

Andrew W Fraley

Marian Gindy

Jennifer Nelson

Victoria Pickering

Ivory Hills

Phieng Siliphaivanh

Joey Lee Methot

Paul A Tempest

Hongbiao Liao

Denise M Kenski

Aarron T Willingham

Lu Tian

Richard W Heidebrecht, Jr

Mark Cancilla

Henry J Haringsma

Craig Alan Coburn

Jongwon Lim

Rob Burke

Thomas Joseph Tucker

Joshua Close

Philip E Sanderson

Rubina G Parmar

Paul E Harrington

David M Tellers

Paul Tempest

William Michael Flanagan

Christopher Hamblett

Kathleen B Calati

Anna A Zabierek

Boyoung Kim

Dawn M Mampreian

Karin M Otte

Amy Rhoden Smith

Njamkou Noucti

Thomas Steele

Harold G Selnick

Michael D Altman

Stephen G Hoge

Bruce D Dorsey

James C Barrow

Alan B Northrup

Shaun R Stauffer

Shawn J Stachel

Philippe G Nantermet

Atanu Roy

Terry A Lyle

Jonathan B Grimm

Wonsuk Chang

Richard Wayne Heidebrecht, Jr

Brandon Mitsuo Taoka

William Joseph Issa

Adel M Naylor-Olsen

Scott C Berk

Daniel Zewge

John Reynders

Vladislav V Telyatnikov

Erin N Guidry

Laura T Kliman

Andrea R Geiser

Zhengwu James Deng

Suresh K Balani

Keith P Moore

Ian Churcher

Jed Hubbs

Mark Cameron

Hua Zhou

Joseph P Vacca

Linghang Zhuang

Mark T Bilodeau

Benito Munoz

Jason David Katz

James Patrick Jewell

Antonin De Fougerolles

Donnette D Staas

Sandra Lee Knowles

Hemaka Anthony Rajapakse

Georgia B McGaughey

Peter Alan Hunt

Jeffrey G Aaronson

Matthew M Morrissette

Sam Kattar

Brian R Fritz

The invention features polynucleotides encoding a polypeptide including a 3'-stabilizing region and having increased stability compared to wild-type polynucleotides.

Polynucleotides containing a stabilizing tail region

The disclosure provides polynucleotides encoding a polypeptide including a morpholino linker. In some embodiments, the polynucleotides of the invention have increased stability compared to wild-type polynucleotides.

Polynucleotides containing a morpholino linker

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against target gene expression.

RNA interference mediated inhibition of gene expression using short interfering nucleic acids (siNA)

The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

Low molecular weight cationic lipids for oligonucleotide delivery

The present disclosure relates to cap analogs, which can result in high levels of capping efficiency and transcription and improved translation efficiencies. The present disclosure also relates to methods useful for preparing cap analogs and using mRNA species containing such analogs, as well as kits containing the novel cap analogs.

Trinucleotide mRNA cap analogs

The present invention relates to RNAi molecules, and compositions thereof, comprising a 2' internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5&#x2032; end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5&#x2032; modified nucleotides that comprise, among other potential modifications, a 2&#x2032; internucleoside linkage. The invention further relates to 5&#x2032; modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

Short interfering nucleic acid (siNA) molecules containing a 2' internucleoside linkage (3dT)

The instant invention provides for novel catiome lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

The present disclosure relates to cap analogs, which can result in high levels of capping efficiency and transcription and improved translation efficiencies. The present disclosure also relates to methods useful for preparing cap analogs and using mRNA species containing such analogs, as well as kits containing the cap analogs.

Phosphate replacement MRNA cap analogs

Phosphate replacement mRNA cap analogs

Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)-(G); wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)-(L)-(G); wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

Dual molecular delivery of oligonucleotides and peptide containing conjugates

The present disclosure provides alternative sugar moieties and polynucleotides comprising such sugar moieties, and methods of use thereof.

Polynucleotide molecules and uses thereof

Growing community of inventors

Marlton, NJ, United States of America

Matthew G Stanton