Cold Spring Harbor Laboratory

The General Hospital Corporation

Sihem Cheloufi

Gregory J Hannon

Konrad Hochedlinger

Marti Anne Borkent

Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Ago2 because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

Structurally designed shRNAs

Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Agog because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

Provided herein are methods for performing cellular reprogramming that include treatment of somatic cells with an inhibitor of CAF-1, Sumo2, Nutd21, or combinations thereof prior to or during a reprogramming procedure. Such inhibitors can improve both the speed and efficiency of cellular reprogramming. Inhibitors of the CAF-1 complex can also be used in the treatment of cancer.

Growing community of inventors

Boston, MA, United States of America

Sihem Cheloufi