Sirna Therapeutics, Inc.

Ribozyme Pharmaceuticals, Incorporated

Merck Sharpe & Dohme Corp.

Peter Haeberli

Leonid Beigelman

Alexander Karpeisky

David Sweedler

Chandra Vargeese

Weimin Wang

Tongqian Chen

Jasenka Matulic-Adamic

Mark Reynolds

James A McSwiggen

James D Thompson

John Min

Nilabh Chaudhary

Tod M Woolf

Nassim Usman

Thale Jarvis

Alex Karpeisky

Shawn Patrick Zinnen

Pamela Pavco

Laurent Bellon

David Morrissey

Bharat Chowrira

Kathy L Fosnaugh

Dennis G Macejak

Narendra K Vaish

Michael Zwick

Vladmir Serebryany

Sharon F Jamison

Vladimir Serebryany

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)

This invention features conjugates, degradable linkers, compositions, methods of synthesis, and applications thereof, including cholesterol, folate, galactose, galactosamine, N-acetyl galactosamine, PEG, phospholipid, peptide and human serum albumin (HSA) derived conjugates of biologically active compounds, including antibodies, antivirals, chemotherapeutics, peptides, proteins, hormones, nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids, DNAzymes, allozymes, antisense, dsRNA, siNA, siRNA, triplex oligonucleotides, 2,5-A chimeras, decoys and aptamers.

Conjugates and compositions for cellular delivery

This invention features conjugates, degradable linkers, compositions, methods of synthesis, and applications thereof, including cholesterol derived conjugates of biologically active compounds, including antibodies, antivirals, chemotherapeutics, peptides, proteins, hormones, nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids, DNAzymes, allozymes, antisense, dsRNA, siNA, siRNA, triplex oligonucleotides, 2,5-A chimeras, decoys and aptamers.

This invention features permeability enhancer molecules, and methods, to increase membrane permeability of various molecules, such as nucleic acids, polynucleotides, oligonucleotides, enzymatic nucleic acid molecules, antisense nucleic acid molecules, 2-5A antisense chimeras, triplex forming oligonucleotides, decoy RNAS, dsRNAs, siRNAs, aptamers, or antisense nucleic acids containing nucleic acid cleaving chemical groups, peptides, polypeptides, proteins, carbohydrates, steroids, metals and small molecules, thereby facilitating cellular uptake of such molecules.

Compositions for the delivery of negatively charged molecules

This invention features conjugates, degradable linkers, compositions, methods of synthesis, and applications thereof, including galactosamine and N-acetyl galactosamine derived conjugates of biologically active compounds, including antibodies, antivirals, chemotherapeutics, peptides, proteins, hormones, nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids, DNAzymes, allozymes, antisense, dsRNA, siNA, siRNA, triplex oligonucleotides, 2,5-A chimeras, decoys and aptamers.

Process for chemical synthesis of methoxy nucleosides.

Chemical synthesis of methoxy nucleosides

The present invention provides methods for the chemical synthesis of nucleosides and derivatives thereof, including 2&prime;-amino, 2&prime;-N-phthaloyl, 2&prime;-O-methyl, 2&prime;-O-silyl, 2&prime;-OH nucleosides, C-nucleosides, nucleoside phosphoramidites, C-nucleoside phosphoramidites, and non-nucleoside derivatives.

Methods for synthesizing nucleosides, nucleoside derivatives and non-nucleoside derivatives

This invention relates to novel chemically-modified nucleic acid molecules having specific formulae that exhibit increased resistance to nucleases and increased binding affinity to target nucleic acid molecules. The invention further relates to methods of modulating gene expression using the novel chemically modified nucleic acid molecules, and compositions and cells comprising said molecules.

Nucleic acid molecules with novel chemical compositions capable of modulating gene expression

This invention features permeability enhancer molecules, and methods, to increase membrane permeability of negatively charged polymers thereby facilitating cellular uptake of such polymers.

Several processes for the chemical synthesis of 2'-O-methoxy purine nucleosides are herein disclosed.

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Berthoud, CO, United States of America

Peter Haeberli