Sangamo Biosciences, Inc.

Amgen Mountain View, Inc.

Qiang Liu

Edward J Rebar

Andrew Jamieson

Stephen P Eisenberg

Eric E Jarvis

Alan P Wolffe

Pei-Qi Liu

Joshua A Silverman

Alice Bakker

Amy N Duguay

Kevin W Moore

Casey Christopher Case

Willem P C Stemmer

George N Cox

Sanjeev Satyal

Guofu Li

Mylavarapu Venkatramesh

D Victor Perlroth

Benjamin M Alba

Candace Swimmer

Richard Smith

Elizabeth J Wolffe

The specificity of binding of a zinc finger to a triplet or quadruplet nucleotide target subsite depends upon the location of the zinc finger in a multifinger protein and, hence, upon the location of its target subsite within a larger target sequence. The present disclosure provides zinc finger amino acid sequences for recognition of triplet target subsites having the nucleotide G in the 5'-most position of the subsite, that have been optimized with respect to the location of the subsite within the target site. Accordingly, the disclosure provides finger position-specific amino acid sequences for the recognition of GNN target subsites. This allows the construction of multi-finger zinc finger proteins with improved affinity and specificity for their target sequences, as well as enhanced biological activity.

Position dependent recognition of GNN nucleotide triplets by zinc fingers

Provided herein are a variety of methods and compositions for regulating angiogenesis, such methods and compositions being useful in a variety of applications where modulation of vascular formation is useful, including, but not limited to, treatments for ischemia and wound healing. Certain of the methods and compositions accomplish this by using various zinc finger proteins that bind to particular target sites in one or more VEGF genes. Nucleic acids encoding the zinc finger proteins are also disclosed. Methods for modulating the expression of one or more VEGF genes with the zinc finger proteins and nucleic acids are also disclosed. Such methods can also be utilized in a variety of therapeutic applications that involve the regulation of endothelial cell growth. Pharmaceutical compositions including the zinc finger proteins or nucleic acids encoding them are also provided.

Regulation of angiogenesis with zinc finger proteins

Disclosed herein are zinc finger proteins that bind to target sites in a plant gamma-tocopherol methyl transferase (GMT) gene; compositions comprising these GMT-targeted zinc finger proteins and methods of making and using such zinc finger proteins. Also disclosed are methods for modulating the alpha-tocopherol content in various plant organs, particularly seeds, in transgenic plants.

Compositions and methods for regulation of plant gamma-tocopherol methyltransferase

Polypeptides comprising monomer domains that bind to IL-6, or portions thereof, are provided.

IL-6 binding proteins

Polypeptides comprising monomer domains that bind to c-MET, or portions thereof, are provided.

c-MET kinase binding proteins

The present invention provides methods for modulating expression of endogenous cellular genes using engineered zinc finger proteins.

Regulation of endogenous gene expression in cells using zinc finger proteins

Disclosed herein are design methods for optimizing the specificity of a binding protein. The methods comprise iterative cycles of rational design, site selection, redesign and site selection of the redesigned molecule.

Iterative optimization in the design of binding proteins

Growing community of inventors

Foster City, CA, United States of America

Qiang Liu