DOE Patents title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: CRISPR protein inhibitors

Abstract

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.

Inventors:
; ; ; ; ;
Issue Date:
Research Org.:
The Broad Institute, Inc., Cambridge, MA (United States); Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States); Univ. of California, Riverside, MA (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH); Defense Advanced Research Projects Agency (DARPA); US Army Research Office (ARO)
OSTI Identifier:
2222337
Patent Number(s):
11760984
Application Number:
16/760,425
Assignee:
The Broad Institute, Inc. (Cambridge, MA); The Brigham and Women's Hospital, Inc. (Boston, MA); The Regents of the University of California (Oakland, CA)
DOE Contract Number:  
SC0010595; SC0010426; AI126239; N66001-17-2-4055; W911NF1610586
Resource Type:
Patent
Resource Relation:
Patent File Date: 10/31/2018
Country of Publication:
United States
Language:
English

Citation Formats

Choudhary, Amit, Cox, Kurt, Maji, Basudeb, Wu, Peng, Subramanian, Hari, and Franco, Elisa. CRISPR protein inhibitors. United States: N. p., 2023. Web.
Choudhary, Amit, Cox, Kurt, Maji, Basudeb, Wu, Peng, Subramanian, Hari, & Franco, Elisa. CRISPR protein inhibitors. United States.
Choudhary, Amit, Cox, Kurt, Maji, Basudeb, Wu, Peng, Subramanian, Hari, and Franco, Elisa. Tue . "CRISPR protein inhibitors". United States. https://www.osti.gov/servlets/purl/2222337.
@article{osti_2222337,
title = {CRISPR protein inhibitors},
author = {Choudhary, Amit and Cox, Kurt and Maji, Basudeb and Wu, Peng and Subramanian, Hari and Franco, Elisa},
abstractNote = {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.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2023},
month = {9}
}

Works referenced in this record:

A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity
journal, June 2012


Multidimensional chemical control of CRISPR–Cas9
journal, October 2016


CRISPR-based self-cleaving mechanism for controllable gene delivery in human cells
journal, December 2014


Small molecule–triggered Cas9 protein with improved genome-editing specificity
journal, April 2015


Structural Basis for the Altered PAM Specificities of Engineered CRISPR-Cas9
journal, March 2016


Structural Basis for the Canonical and Non-canonical PAM Recognition by CRISPR-Cpf1
journal, August 2017


Ligand-binding domains of nuclear receptors facilitate tight control of split CRISPR activity
journal, July 2016


DNA interrogation by the CRISPR RNA-guided endonuclease Cas9
journal, January 2014


High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells
journal, June 2013


Cas9 specifies functional viral targets during CRISPR–Cas adaptation
journal, February 2015


In vitro fluorescence polarization assay
patent, March 2001


Estimating Protein−Ligand Binding Affinity Using High-Throughput Screening by NMR
journal, November 2008


Fluorescence polarization analysis of protein-DNA and protein-protein interactions
journal, June 1996


Rational design of a split-Cas9 enzyme complex
journal, February 2015


Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA
journal, February 2014


Fragment-based domain shuffling approach for the synthesis of pyran-based macrocycles
journal, March 2011


PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing
journal, December 2015


An Aldol-Based Build/Couple/Pair Strategy for the Synthesis of Medium- and Large-Sized Rings: Discovery of Macrocyclic Histone Deacetylase Inhibitors
journal, December 2010


Chemical and Biophysical Modulation of Cas9 for Tunable Genome Engineering
journal, February 2016


Disabling Cas9 by an anti-CRISPR DNA mimic
journal, July 2017


A High-Throughput Platform to Identify Small-Molecule Inhibitors of CRISPR-Cas9
journal, May 2019


Structure and Engineering of Francisella novicida Cas9
journal, February 2016


The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability
journal, September 2007


Indium‐Mediated Asymmetric Allylation of Acylhydrazones Using a Chiral Urea Catalyst
journal, February 2007


Engineered CRISPR-Cas9 nucleases with altered PAM specificities
journal, June 2015


Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA
journal, January 2016


A Broad-Spectrum Inhibitor of CRISPR-Cas9
journal, September 2017


Inactivation of CRISPR-Cas systems by anti-CRISPR proteins in diverse bacterial species
journal, June 2016


Crystal Structure of Staphylococcus aureus Cas9
journal, August 2015


Naturally Occurring Off-Switches for CRISPR-Cas9
journal, December 2016


A split-Cas9 architecture for inducible genome editing and transcription modulation
journal, February 2015


An iCRISPR Platform for Rapid, Multiplexable, and Inducible Genome Editing in Human Pluripotent Stem Cells
journal, August 2014


Synthesis and Profiling of a Diverse Collection of Azetidine-Based Scaffolds for the Development of CNS-Focused Lead-like Libraries
journal, August 2012


Integrase-mediated spacer acquisition during CRISPR–Cas adaptive immunity
journal, February 2015


High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity
journal, August 2013


CRISPR/Cas9‐mediated genome engineering: An adeno‐associated viral (AAV) vector toolbox
journal, October 2014


Structural Basis for the Altered PAM Recognition by Engineered CRISPR-Cpf1
journal, July 2017


Inhibition of CRISPR-Cas9 with Bacteriophage Proteins
journal, January 2017


A universal method for sensitive and cell-free detection of CRISPR-associated nucleases
journal, January 2019


A Planning Strategy for Diversity-Oriented Synthesis
journal, January 2004