The General Hospital Corporation

Beam Therapeutics Inc.

Jason Michael Gehrke

J Keith Joung

James Angstman

Benjamin Kleinstiver

Shengdar Q Tsai

Michael S Packer

Nicole Marie Gaudelli

Rebecca Tayler Cottman

John Evans

Yi Yu

Bernd Zetsche

Ian Slaymaker

Seung-Joo Lee

David A Born

Natalie Petrossian

Angelica Messana

David Bryson

Yvonne Aratyn

Yanfang Fu

Francine Gregoire

Genesis Lung

Shaunna Berkovitch

Keith J Joung

The invention features compositions and methods for modifying a polynucleotide (e.g., DNA) using a nucleobase editor comprising a first DNA binding protein domain that is catalytically inactive, a domain having base editing activity, and a second DNA binding protein domain having nickase activity. The invention also features a fusion protein comprising a domain having base editing activity (e.g., cytidine deaminase or adenosine deaminase), and two nucleic acid programmable DNA binding protein domains (napDNAbp), a first napDNAbp comprising nickase activity and a second napDNAbp that is catalytically inactive, where at least the two napDNAbps are joined by a linker, as well as related methods for using such base editors, and kits comprising the base editors.

Compositions and methods for improving base editing

The present invention relates to methods to improve the absolute rate of homology-directed repair (HDR) and/or to improve the relative rate of HDR compared with non-homologous end joining (NHEJ).

Methods for increasing efficiency of nuclease-induced homology-directed repair

Provided herein are compositions and methods of using base editors comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain in conjunction with a guide polynucleotide. Also provided herein are base editor systems for editing nucleobases of target nucleotide sequences.

Methods of substituting pathogenic amino acids using programmable base editor systems

Methodologies to detect off-target mutations induced by the deaminase activity of Base Editing technology.

Methods for detecting site-specific and spurious genomic deamination induced by base editing technologies

Methods and compositions for improving the genome-wide specificities of targeted base editing technologies.

Base editors with improved precision and specificity

The disclosure provides compositions comprising novel adenosine base editors (e.g., ABE8) that have increased efficiency and methods of using these adenosine deaminase variants for editing a target sequence.

Adenosine deaminase base editors and methods of using same to modify a nucleobase in a target sequence

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Cambridge, MA, United States of America

Jason Michael Gehrke