Merck Sharp + Dohme Corp.

Aimee L Jackson

Peter S Linsley

Julja Burchard

Steven Bartz

Lee Lim

Guy L Cavet

Michele A Cleary

Jill F Magnus

Gregory J Hannon

Scott William Lowe

Lin He

Janell M Schelter

Xingyue He

Ge Wei

Wei Ge

Steven R Bartz

The invention provides methods and compositions for gene silencing by RNA interference. In particular, the invention provides methods for gene silencing or RNA knockdown using small interfering RNAs (siRNAs) having partial sequence homology to its target gene. The invention also provides methods for identifying common and/or differential responses to a plurality of different siRNAs targeting a gene. The invention also provides methods for evaluating the relative activity of the two strands of an siRNA. The invention further provides methods of designing siRNAs for gene silencing. The invention further provides methods of using siRNAs as therapeutics for treatment of diseases.

Methods and compositions for RNA interference

The present invention provides a method for identifying siRNA target motifs in a transcript using a position-specific score matrix approach. The invention also provides a method for identifying off-target genes of an siRNA using a position-specific score matrix approach. The invention further provides a method for designing siRNAs with higher silencing efficacy and specificity. The invention also provides a library of siRNAs comprising siRNAs with high silencing efficacy and specificity.

Method for selecting SIRNAs from a plurality of SIRNAs for gene silencing

In one aspect, the invention generally relates to use of miR-34 as a biomarker to estimate TP53 function in a cell. In another aspect, the invention generally relates to multiple uses of miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.

Methods of using MIR34 as a biomarker for TP53 functional status

In one aspect, the invention generally relates to compositions comprising miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.

Compositions comprising MIR34 therapeutic agents for treating cancer

Method of designing siRNAs for gene silencing

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Seattle, WA, United States of America

Aimee L Jackson