Phio Pharmaceuticals Corp.

Rxi Pharmaceuticals Corporation

Life Technologies Corporation

Other

X-body, Inc.

Oligos Etc. Inc.

Harvard College

Curis, Inc.

Sirna Therapeutics, Inc.

Lakewood Amedex, Inc.

Sequitur, Inc.

Etagen Pharma, Inc.

Rxi Parmaceuticals Corporation

Ipifini, Inc.

Hogrefe, Richard I.

Tod M Woolf

Anastasia Khvorova

Joanne Kamens

William Salomon

Dmitry Samarsky

James Cardia

Pamela A Pavco

Lyn Libertine

Karen G Bulock

Margaret Taylor

Amy Arrow

Yan Chen

Richard W Wagner

Douglas A Melton

Roderic M K Dale

Kristin Wiederholt

Ping Jin

Jonathan M Graff

Michelle Miller

Leonid Beigelman

James A McSwiggen

Jasenka Matulic-Adamic

Alexander Karpeisky

Thale Jarvis

James D Thompson

Richard I Hogrefe

Alexandre Lebedev

Peter Haeberli

Laurent Bellon

Mark Reynolds

Roderic M Dale

Roderic Mk Dale

Scott Neumann

Michael Zwick

Andrew S Marks

Alexandre V Lebedev

Scott Woolf

Glenn Wachler

Margaret F Taylor

Karen Gunn Bulock

Kristin A Wiederholt

The present invention includes compositions and methods for the treatment of a medical condition or disease utilizing editing oligonucleotides. The editing oligonucleotides contain an oligonucleotide strand of about 10 to about 50 nucleotides on each side of the editing moiety which may contain a sugar or linker that positions the active editing moiety in the proper location for hybridization to the target nucleic acid. The editing oligonucleotides may also contain at least one nucleotide sequence change from the targeted sequence in the genome. The method includes modifying a genomic sequence within a cell utilizing an editing oligonucleotide without additional proteins or nucleic acids to assist in the editing process. The editing oligonucleotide may comprise backbone modifications that increase the nuclease stability of the oligonucleotide as compared to unmodified oligonucleotides or oligonucleotides having three phosphorothioates on each terminus.

Compositions and methods for editing nucleic acids in cells utilizing oligonucleotides

The present invention relates to RNAi constructs and their use in gene silencing. RNAi constructs associated with the invention contain a double stranded region connected to a single stranded region of phosphorothioate modified nucleotides.

RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality

Provided are methods and compositions for the production of novel antibodies that bind specifically to a target antigen. These methods and compositions are particularly useful for producing antibodies having the antigen binding specificity of a reference antibody but with improved properties (e.g., binding affinity, immunogenicity, and thermodynamic stability) relative to the reference antibody.

Antibody screening methods

The present invention relates to ocular administration of sd-rxRNA and rxRNAori molecules.

RNA interference in ocular indications

Neutral lipid formulations for nucleic acid delivery are provided according to the invention. The neutral lipid formulations include hydrophobically modified polynucleotides and fat mixtures. Methods of using the neutral lipid formulations are also provided.

Neutral nanotransporters

RNAi constructs directed to MAP4K4 that demonstrate unexpectedly high gene silencing activities, and uses thereof are disclosed. The blunt-ended constructs have a double-stranded region of 19-49 nucleotides. The constructs have selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the strands may be modified (e.g., one or both ends of the sense strand is modified by 2'-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, the antisense strand may also be modified by a 2&#x2032;-O-methyl group at the penultimate 5&#x2032;-end nucleotide to greatly reduce off-target silencing.

Inhibition of MAP4K4 through RNAi

The present invention relates to methods for in vivo administration of sd-rxRNA molecules.

Reduced size self-delivering RNAI compounds

The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal and fibrotic applications.

RNA interference in dermal and fibrotic indications

The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing. The RNAi constructs may be, for instance, miRNA constructs that are miRNA modulators.

The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications.

RNA interference in skin indications

The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing.

The invention related to improved RNAi constructs and uses thereof. The construct has a double stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferable blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified (e.g., one or both ends of the sense strand it/are modified by four 2'&#x2014;O-mehtyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2&#x2032;&#x2014;O-methyl group at the 2nd 5&#x2032;-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhance target specificity.

Modified RNAi polynucleotides and uses thereof

The oligonucleotide compositions of the present invention make use of combinations of oligonucleotides. In one aspect, the invention features an oligonucleotide composition including at least 2 different oligonucleotides targeted to a target gene. This invention also provides methods of inhibiting protein synthesis in a cell and methods of identifying oligonucleotide compositions that inhibit synthesis of a protein in a cell.

Oligonucleotide compositions with enhanced efficiency

Growing community of inventors

Sudbury, MA, United States of America

Tod M Woolf