Sirna Therapeutics, Inc.

Resolution Bioscience, Inc.

Merck Sharp + Dohme Corp.

Lee Lim

Christopher K Raymond

Guillaume Chorn

Lihong Zhao

Christopher D Armour

Peter S Linsley

Julja Burchard

Aarron T Willingham

Aimee L Jackson

Michele A Cleary

Jill F Magnus

Gregory J Hannon

Scott William Lowe

Janell M Schelter

Lin He

Xingyue He

Jennifer Hernandez

Miho Kibukawa

The invention provides a method for genetic analysis in individuals that reveals both the genetic sequences and chromosomal copy number of targeted and specific genomic loci in a single assay. The present invention further provides methods for the sensitive and specific detection of target gene sequences and gene expression profiles.

Methods for quantitative genetic analysis of cell free DNA

The invention provides a method for genetic analysis in individuals that reveals both the genetic sequences and chromosomal copy number of targeted and specific genomic loci in a single assay. The present invention further provide methods for the sensitive and specific detection of target gene sequences and gene expression profiles.

Methods for targeted genomic analysis

The invention provides a method for efficient DNA library construction and targeted genetic analyses of the libraries.

High efficiency construction of DNA libraries

The present invention includes compositions and methods useful for the detection of a mutational change, SNP, translocation, inversion, deletion, change in copy number, or other genetic variation within a sample of cellular genomic DNA or cell-free DNA (cfDNA). In some embodiments, the compositions and methods of the present invention provide an extremely high level of resolution that is particularly useful in detecting copy number variations in a small fraction of the total cfDNA from a biological sample (e.g., blood).

Methods for the detection of genomic copy changes in DNA samples

The instant disclosure features single-stranded RNA molecules comprising one or more internal, non-nucleotide spacers. A non-nucleotide spacer covalently links nucleotide portions of the molecule. The single-stranded RNA molecules function as guide or antisense strands that are capable of inhibiting gene expression via an RNA interference mechanism and, thus, represent single-stranded RNAi agents. The single-stranded RNAi molecules can be used in methods for a variety of therapeutic, diagnostic, target validation, genomic discovery, genetic engineering, and pharmacogenomic applications.

Single-stranded RNAi agents containing an internal, non-nucleic acid spacer

This invention relates generally to segmented oligonucleotides capable of modulating gene expression. Specifically, the instant invention relates to segmented microRNA (miRNA) oligonucleotides, including segmented miRNA precursors and segmented pre-microRNAs. The invention also relates to compositions comprising such segmented oligonucleotides, as well as to methods of making and using such oligonucleotides for diagnosis and treatment of diseases associated or causally linked to aberrant levels or activities of gene expression, including aberrant levels of coding and/or non-coding RNA.

Segmented micro RNA mimetics

Single-stranded RNA molecules comprise one or more internal, non-nucleotide spacers, covalently linked with nucleotide portions of the molecule are provided. The single-stranded RNA molecules function as guide or antisense strands that are capable of inhibiting gene expression via an RNA interference mechanism, and thus represent single-stranded RNAi agents. The single-stranded RNAi molecules can be used in methods for a variety of therapeutic, diagnostic, target validation, genomic discovery, genetic engineering, and pharmacogenomic applications.

In one aspect, a method is provided of inhibiting proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one at least one small interfering RNA agent (iRNA), wherein said iRNA comprises a nucleotide sequence of at least 15 nucleotides, wherein the nucleotide sequence comprises a seed region consisting of nucleotide positions 1 to 12, wherein position 1 represents the 5' end of the iRNA nucleotide sequence and wherein said seed region comprises a nucleotide sequence of at least six contiguous nucleotides that is complementary to six contiguous nucleotides within positions 1 to 12 of a nucleotide sequence, wherein position 1 represents the 5&#x2033;end of the nucleotide sequence, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8. In some embodiments, the method comprises introducing at least one iRNA that inhibits the expression of at least one miR-16 responsive gene selected from TABLE 5 into the mammalian cell.

Methods and compositions for regulating cell cycle progression

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.

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San Francisco, CA, United States of America

Lee Lim