Sangamo Therapeutics, Inc.

Sangamo Biosciences, Inc.

Dow Agrosciences LLC

University of Minnesota

Russell DeKelver

Fyodor Urnov

Philip D Gregory

Edward J Rebar

Jeffrey C Miller

David Paschon

H Steve Zhang

Gregory J Cost

Andreas Reik

Jianbin Wang

Anthony Conway

Phillip Tam

Michael C Holmes

Manju Gupta

Joseph F Petolino

Stephen N Novak

Lei Zhang

R Scott McIvor

Thomas Wechsler

Ivan Krivega

Kanut Laoharawee

Chester B Whitley

Li Ou

Described herein are engineered nucleases comprising mutations in the cleavage domain (e.g., FokI or homologue thereof) and/or DNA binding domain (zinc finger protein, TALE, single guide RNA) such that on-target specificity is increased.

Engineered target specific nucleases

Methods and compositions comprising a CRISPR/Cas nuclease that cleaves a BCL11A gene for the modification of the BCL11A gene and for modification of globin expression.

Methods and compositions for treatment of a genetic condition

Methods and compositions comprising a CRISPR/Cas nuclease that cleaves a T cell receptor (TCR) gene and/or human leukocyte (HLA) gene, the nuclease comprising a cleavage domain and a single guide RNA that binds to a target site in the TCR and/or HLA gene.

The present disclosure relates to engineered zinc finger proteins that target genes in plants involved in fatty acid biosynthesis. Methods of using such zinc finger proteins in modulating gene expression, gene inactivation, and targeted gene modification are also provided.

Engineered zinc finger proteins targeting plant genes involved in fatty acid biosynthesis

Disclosed herein are methods and compositions for targeted integration of an exogenous sequence into the human PPP1R12C locus, for example, for expression of a polypeptide of interest.

Targeted integration into the PPP1R12C locus

Methods and compositions comprising a fusion protein comprising a Cas protein and a functional domain in association with a single guide RNA targeted to an endogenous gene for genetic alteration of cells are provided.

Methods and compositions comprising single guide RNAs targeted to an endogenous mammalian &#x3b2; globin gene (HBB), gamma globin gene (HBG1), B-cell lymphoma/leukemia 11A (BCL11A) gene, Kruppel-like factor 1 (KLF1) gene, CCR5 gene, CXCR4 gene, PPP1R12C (AAVS1) gene, hypoxanthine phosphoribosyltransferase (HPRT) gene, albumin gene, Factor VIII gene, Factor IX gene, Leucine-rich repeat kinase 2 (LRRK2) gene, Hungtingin (Htt) gene, rhodopsin (RHO) gene, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, surfactant protein B gene (SFTPB), T-cell receptor alpha (TRAC) gene, T-cell receptor beta (TRBC) gene, programmed cell death 1 (PD1) gene, Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene, human leukocyte antigen (HLA) A gene, a LMP7 gene, a Transporter associated with Antigen Processing (TAP) gene, tapasin gene (TAPBP), a class II major histocompatibility complex transactivator (CIITA) gene, a dystrophin gene (DMD), a glucocorticoid receptor gene (GR), IL2RG gene or RFX5 for genetic alteration of cells are provided.

Disclosed herein are linear donor molecules comprising homology arms of 50-750 base pairs (e.g., 50-100 base pairs) flanking one or more sequences of interest. The donor molecules and/or compositions comprising these molecules can be used in methods for targeted integration of an exogenous sequence into a specified region of interest in the genome of a cell.

Linear donor constructs for targeted integration

Disclosed herein are linear donor molecules comprising homology arms of 50-750 base pairs (e.g., 50-100 base pairs) flanking one or more sequences of interest. The donor molecules and/or compositions comprising these molecules can be used in methods for integration of an exogenous sequence into a specified region of interest in the genome of a cell.

Growing community of inventors

Richmond, CA, United States of America

Russell DeKelver