Leland Stanford Junior University

Vertex Pharmaceuticals, Inc.

Agilent Technologies, Inc.

University and Agilent Technologies, Inc.

University of Texas System

Crispr Therapeutics Ag

Boco Silicon Valley, Inc.

Matthew Hebden Porteus

Ayal Hendel

Daniel E Ryan

Douglas J Dellinger

Mark A Kay

Joel Myerson

Robert Kaiser

Waracharee Srifa

Kazuya Ikeda

Ante Sven Lundberg

Nobuko Uchida

Ann Tsukamoto

Rasmus O Bak

Daniel P Dever

Joe Clark

Chad Albert Cowan

Michelle I-Ching Lin

Jeffrey Li

Thao Thi Nguyen

Adi Barzel

Joseph T Clark

Sriram Vaidyanathan

Alice Bertaina

Volker Andreas Wiebking

Melanie Ruth Allen

Eric J Kildebeck

Josh Checketts

Jenny Barker

Richard Voit

A method for scarless genome editing is disclosed. In particular, the method provides scarless genome modification by using homology directed repair (HDR) steps to genetically modify cells and remove unwanted sequences. This method can be used for genome editing, including introducing mutations, deletions, or insertions at any position in the genome without leaving silent mutations, selection marker sequences, or other additional undesired sequences in the genome.

Scarless genome editing through two-step homology directed repair

The present application provides materials and methods for treating hemoglobinopathies. More specifically, the application provides methods for producing progenitor cells that are genetically modified via genome editing to increase the production of fetal hemoglobin (HbF), as well as modified progenitor cells (including, for example, CD34human hematopoietic stem cells) producing increased levels of HbF, and methods of using such cells for treating hemoglobinopathies such as sickle cell anemia and β-thalassemia.

Materials and methods for treatment of hemoglobinopathies

Materials and methods for treatment of human genetic diseases including hemoglobinopathies

Methods and compositions for modifying allogeneic donor αβ T cells for use in the treatment of high risk leukemias are provided.

Genome editing of graft-derived T-cells for post-transplant immunotherapy

Provided herein are methods for inducing CRISPR/Cas-based gene regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using modified single guide RNAs (sgRNAs) that enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a modified sgRNA to correct a mutation in a target gene associated with the genetic disease.

Compositions comprising chemically modified guide RNAs for CRISPR/Cas-mediated editing of HBB

The present invention relates to a system and method for efficiently modifying the genome of cells to treat diseases via sequential homologous recombination using CRISPR/Cas-mediated genome editing with donor DNA delivered by two or more adeno-associated virus (AAV) vectors.

CRISPR/Cas 9-mediated integration of polynucleotides by sequential homologous recombination of AAV donor vectors

In certain aspects, the present invention provides methods for inducing a stable gene modification of a target nucleic acid via homologous recombination in a primary cell, such as a primary blood cell and/or a primary mesenchymal cell. In certain other aspects, the present invention provides methods for enriching a population of genetically modified primary cells having targeted integration at a target nucleic acid. The methods of the present invention rely on the introduction of a DNA nuclease such as a Cas polypeptide and a homologous donor adeno-associated viral (AAV) vector into the primary cell to mediate targeted integration of the target nucleic acid. Also provided herein are methods for preventing or treating a disease in a subject in need thereof by administering to the subject any of the genetically modified primary cells or pharmaceutical compositions described herein to prevent the disease or ameliorate one or more symptoms of the disease.

Pharmaceutical compositions comprising gene-corrected primary cells

Chemically modified guide RNAS for CRISPR/Cas-mediated gene regulation

Nuclease-mediated genome editing of primary cells

Chemically modified guide RNAs for CRISPR/CAS-mediated gene regulation

Nuclease-mediated genome editing of primary cells and enrichment thereof

The present application provides materials and methods for treating hemoglobinopathies. More specifically, the application provides methods for producing progenitor cells that are genetically modified via genome editing to increase the production of fetal hemoglobin (HbF), as well as modified progenitor cells (including, for example, CD34human hematopoietic stem cells) producing increased levels of HbF, and methods of using such cells for treating hemoglobinopathies such as sickle cell anemia and &#x3b2;-thalassemia.

Growing community of inventors

Stanford, CA, United States of America

Matthew Hebden Porteus