The Brigham and Women's Hospital, Inc.

The Broad Institute, Inc.

University of California

Harvard College

Massachusetts Institute of Technology

Amit Choudhary

Kurt Cox

Basudeb Maji

Elisa Franco

Soumyashree Ashok Gangopadhyay

Miseon Lee

Peng Wu

Hari Subramanian

Debasish Manna

Feng Zhang

Bernd Zetsche

Bridget K Wagner

Praveen Tiwari

Peter Jones

Ashley Modell

Sameek Singh

Uttam Dhawa

Santosh Chaudhary

Prashant Singh

Mengchao Shi

Veronika Shoba

Donghyun Lim

Vika Anokhina

Kisuk Yang

Hari K K Subramanian

3D cell cultures and devices for 3D cell culture, and methods of use thereof are provided. In some embodiments, the 3D cell culture comprise pancreatic β cells and can be generated in multi-well plates, allowing for high throughput assays on the cell culture.

Three-dimensional cell culture, devices, and use thereof

Compositions and methods are provided for the inhibition of the function of RNA guided endonucleases, including the identification and use of such inhibitors. Methods of identifying inhibitor compounds of RNA guided nucleases, assays for detecting nuclease activity and compounds for use therein are also provided.

Inhibitors of RNA-guided nuclease activity and uses thereof

The disclosure includes non-naturally occurring or engineered CRISPR Cas9, each associated with at least one destabilization domain (DD), along with compositions, systems and complexes involving the DD-CRISPR Cas9, nucleic acid molecules and vectors encoding the same, delivery systems involving the same, uses therefor.

CRISPR having or associated with destabilization domains

The disclosure includes non-naturally occurring or engineered DNA- or RNA-guided nuclease systems, comprising CRISPR enzymes associated with at least one destabilization domain (DD) and photocaged stabilization ligands with at least one photocage molecule, along with compositions, systems and complexes involving such systems, nucleic acid molecules and vectors encoding the same, delivery systems involving the same, uses thereof.

Methods and compositions for optochemical control of CRISPR-CAS9

The present disclosure relates to chimeric small molecules, which find utility as modifiers of target substrates according to the formula A-L-E-B or A-L-E-L-B, wherein A is a kinase binding moiety; B is a target binding moiety; Land Lare each a linker; and E is an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post-translational modifications to targets that are not the natural substrate of the kinase; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.

Bifunctional chimeric molecules for labeling of kinases with target binding moieties and methods of use thereof

Compositions and methods for inhibiting the activity of RNA-guided endonucleases, and methods for identifying such compositions are included. Methods of treatment using the inhibitory compounds, formulations and methods are also detailed, as well as control of nucleic acid editing systems and methods using said compounds.

Inhibitors of RNA-guided nuclease target binding and uses thereof

The present inventions generally relate to site-specific delivery of nucleic acid modifiers and includes novel DNA-binding proteins and effectors that can be rapidly programmed to make site-specific DNA modifications. The present inventions also provide a synthetic all-in-one genome editor (SAGE) systems comprising designer DNA sequence readers and a set of small molecules that induce double-strand breaks, enhance cellular permeability, inhibit NHEJ and activate HDR, as well as methods of using and delivering such systems.

Nucleic acid modifiers

The disclosure includes zinc prodrugs for targeted delivery of therapeutic, diagnostic or imaging agents to β-cells and methods of use therefor. The disclosure also includes targeted delivery of small molecules to β-cells that stabilize and activate CRISPR effector proteins comprising at least one destabilization domain, to enable CRISPR-based genome editing and transcriptional activation or repression in β-cells.

Targeted delivery to beta cells

Compositions and methods for conditionally regulating activities of CRISPR-Cas systems. In some embodiments, the methods comprise providing an inactive guide RNA comprising a regulatory domain bound by a lock nucleic acid different from the guide RNA; and displacing the lock nuclei acid from the regulatory domain by a trigger nucleic acid, thereby activating the guide RNA, wherein the activated guide RNA forms a complex with a Cas enzyme.

Compositions and methods for regulating proteins and nucleic acids activities

Compositions and methods are provided for the inhibition of the function of RNA guided endonucleases, including the identification and use of such inhibitors.

Inhibitors of RNA guided nucleases and uses thereof

The embodiments disclosed herein utilize fluorescence polarization based preliminary screen to identify a putative set of Cas inhibitors from an initial set of candidate inhibitors. The primary screening assay is followed by secondary screening assay to validate the putative set of inhibitors selected by the preliminary screen. In some embodiments, the present disclosure includes compositions and methods are provided for the inhibition of the function of RNA guided endonucleases, including the identification and use of such inhibitors.

Growing community of inventors

Boston, MA, United States of America

Amit Choudhary