Massachusetts Institute of Technology

Yale University

The Broad Institute, Inc.

Sidi Chen

Feng Zhang

Phillip A Sharp

Matthew Dong

Neville Espi Sanjana

Randall Jeffrey Platt

Lupeng Ye

Jonathan Park

Ryan D Chow

Guangchuan Wang

Feifei Zhang

The present invention includes compositions and methods for identification of membrane targets for enhancement of T cell activity against a disease, disorder or condition, and/or enhancing T cell anti-tumor activity in a subject in need thereof. In some embodiments, the disease is cancer. In further embodiments, the cancer is glioblastoma (GBM) or breast cancer.

Compositions for identification of membrane targets for enhancement of T cell activity against cancer

The present invention relates to in vivo methods for modeling tumor formation and/or tumor evolution comprising the use of eukaryotic cells in which one or more genetic target locus has been altered by the CRISPR/Cas system, and which cells are transplanted in non-human eukaryote as a model system for tumor formation and tumor evolution. In particular in vivo genetic screening methods for identifying genes involved in tumorigenesis and metastasis are disclosed. The invention further relates to kits and components for practicing the methods, as well as materials obtainable by the methods, in particular tumor and metastasis samples and cells or cell lines derived therefrom. The invention also relates to diagnostic and therapeutic methods derived from the information obtained in the modeling methods.

CRISPR mediated in vivo modeling and genetic screening of tumor growth and metastasis

The present invention includes compositions and methods for T cell genome editing and screening in vivo. In certain aspects, the invention includes an sgRNA library for genome-scale mutagenesis.

Platform for T lymphocyte genome engineering and in vivo high-throughput screening thereof

The invention involves inducing 3-50 or more mutations (e.g., any whole number between 3 and 50 of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such as AAV, and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model genetic disease, e.g. cancer. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., cancer.

Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for modeling competition of multiple cancer mutations in vivo

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Milford, CT, United States of America

Sidi Chen