University of California

Sirius Therapeutics, Inc.

Tallac Therapeutics, Inc.

Tollnine, Inc.

Bryan R Meade

Sukumar Sakamuri

Son Lam

Laxman Eltepu

Bin Liu

Curt William Bradshaw

Dingguo Liu

Steven F Dowdy

Ayman Kabakibi

Joseph Stock

Giuseppe Dello Iacono

Edward Hyungsuk Ha

Jehangir Wadia

Curt W Bradshaw

Scott G Petersen

Akiko Eguchi

Khirud Gogoi

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use

Disclosed are polynucleotide constructs having a strand linked to a moiety carrying one or more auxiliary moieties. Also disclosed are polynucleotide constructs interrupted with a sugar analogue, and polynucleotide constructs with stereochemical{circumflex over ( )} enriched phosphorothioates. The polynucleotide constructs may be provided as hybridized polynucleotide constructs. Also featured are methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell by contacting the cell with the disclosed polynucleotide construct or hybridized polynucleotide construct.

Polynucleotide constructs

The disclosure provides methods and compositions for delivering polynucleotides into cells. The disclosure provides transiently protected polynucleotides comprising an anionic charge-neutralizing moiety/group, which may also confer additional functionality. These compounds can enter the cytosol of cells by endocytic or macropinocytic mechanisms. The transient protecting group is bioreversible, i.e., once inside a cell, it is designed to be removed by enzymatic activity or by passive intracellular methods (e.g., changes in pH or reductive environment).

Polynucleotides having bioreversible groups

The disclosure provides fusion polypeptides and constructs useful in delivering anionically charged nucleic acid molecules including diagnostics and therapeutics to a cell or subject. The fusion constructs include a protein transduction domain and a nucleic acid binding domain, or a protein transduction domain and a nucleic acid that is coated with one or more nucleic acid binding domains sufficient to neutralize an anionic charge on the nucleic acid. Also provided are methods of treating disease and disorders such as cell proliferative disorders.

Transducible delivery of siRNA by dsRNA binding domain fusions to PTD/CPPS

Growing community of inventors

San Diego, CA, United States of America

Bryan R Meade