Alnylam Pharmaceuticals, Inc.

Wyeth

Nucleonics, Inc.

Chandrasekhar Satishchandran

Catherine Julia Pachuk

Liat Mintz

Vincent R Zurawski

Tony Giordano

Daniel E McCallus

Shankar Musunuri

Martin D Sigg, Jr

Daniel E Mccallus

Catherine J C/o Nucleonics Inc Pachuk

Martin D Sigg

Conserved consensus sequences from known hepatitis B virus strains and known hepatitis C virus strains, which are useful in inhibiting the expression of the viruses in mammalian cells, are provided. These sequences are useful to silence the genes of HBV and HCV, thereby providing therapeutic utility against HBV and HCV viral infection in humans.

Conserved HBV and HCV sequences useful for gene silencing

Described herein are methods for identifying nucleic acid sequences that modulate the function of a cell, the expression of a gene in a cell, or the biological activity of a target polypeptide in a cell. The methods involve the use of double stranded RNA expression libraries, double stranded RNA molecules, and post-transcriptional gene silencing techniques.

Post-transcriptional gene silencing using expressed double stranded RNA

Expression constructs comprising at least two different RNA polymerase III promoters, wherein each promoter is operably linked to a nucleic acid sequence encoding an RNA effector molecule, are disclosed herein. Further provided are expression constructs comprising multiple polymerase III promoters operably linked to sequences encoding short hairpin RNA molecules, which may comprise single and/or multiple fingers. The provided constructs are useful for in vivo delivery of RNA molecules effective in gene silencing, including of viral genes including HBV and HCV.

Multiple RNA polymerase III promoter expression constructs

The invention features methods of analyzing the kinetics properties of transfection reactions. Also featured are methods for creating structural promoters which are effectively unregulated by enhancers and repressors. The structural promoters are significantly more active than the native promoter sequences upon which they are based.

Transfection kinetics and structural promoters

A soluble ionic complex is formed by an aqueous mixture of a benzylammonium group-containing surfactant and a polynucleic acid sequence. When the mixture forms a vesicular complex, the sequence is packaged therein. This composition is useful in pharmaceutical compositions and in methods of delivering the polynucleic acid sequence (which preferably encodes a protein or peptide) to a cell for expression. Such methods are useful in therapy, as vaccines and as gene therapy agents.

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Cambridge, MA, United States of America

Chandrasekhar Satishchandran