Massachusetts Institute of Technology

The Broad Institute, Inc.

Harvard College

Beam Therapeutics Inc.

The Board Institute, Inc.

Bernd Zetsche

Feng Zhang

Ian Slaymaker

Omar O Abudayyeh

Jonathan S Gootenberg

Yi Yu

Nicole Marie Gaudelli

Michael S Packer

Seung-Joo Lee

David A Born

Linyi Gao

Winston X Yan

Neville Espi Sanjana

David Benjamin Turitz Cox

Sara Jones

Johnathan S Gootenberg

Fei Ran

James E Dahlman

Amit Choudhary

Jason Michael Gehrke

Michael Packer

Omar Abudayyeh

Jonathan Strecker

Francine Gregoire

Genesis Lung

Shaunna Berkovitch

Natalie Petrossian

Angelica Messana

Yvonne Aratyn

Nicole Gaudelli

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 invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

CRISPR enzymes and systems

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Aspects of the invention in particular relate to Cpf1 mutants having altered PAM specificity.

CRISPR enzymes and systems with modified pam specificity

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

CPF1 complexes with reduced indel activity

Disclosed and claimed are mutation(s) or modification(s) of the CRISPR enzyme, for example a Cas enzyme such as a Cas9, which obtain an improvement, for instance a reduction, as to off-target effects of a CRISPR-Cas or CRISPR-enzyme or CRISPR-Cas9 system or complex containing or including such a mutated or modified Cas or CRISPR enzyme or Cas9. Methods for making and using and uses of such mutated or modified Cas or CRISPR enzyme or Cas9 and systems or complexes containing the same and products from such methods and uses are also disclosed and claimed.

CRISPR enzyme mutations reducing off-target effects

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

Crispr enzymes and systems

The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed 'ABE8' having unprecedented levels (e.g., >60-70%) of efficiency.

Compositions and methods for treating hemoglobinopathies

The invention provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a DNA-targeting Cpf1 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.

Systems, methods, and compositions for targeted nucleic acid editing

The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed 'ABE8' having unprecedented levels (e.g., &#x3e;60-70%) of efficiency.

Growing community of inventors

Gloucester, MA, United States of America

Bernd Zetsche