Dana-farber-cancer Institute Inc.

The Broad Institute, Inc.

Massachusetts Institute of Technology

Rameen Beroukhim

Paul Blainey

David Feldman

Pratiti Bandopadhayay

Funien Tsai

Todd R Golub

Cory M Johannessen

Oana Enache

Uri Ben-david

Veronica Rendo

Cory Johannessen

The subject matter disclosed herein is generally directed to methods and compositions for tagging cells of interest, tracking evolution of the tagged cells, and recovering the original tagged cells for further study. Specifically, cells are tagged with a DNA construct encoding a barcode sequence comprising a guide sequence. Barcoded cells can then be recovered using a reporter construct having CRISPR target sequences specific for the cell having a barcode of interest.

Methods and compositions for studying cell evolution

Described herein are embodiments of methods to rationally design CRISPR-Cas system-based therapeutics and therapies based on expression of a DNA-damage response signature in a cell. In some embodiments, the methods include screening a set of CRISPR-Cas systems by expressing each CRISPR-Cas system in a test cell population and modifying one or more target sequences in the test cell population; screening in the test cell population for each CRISPR-Cas system and expression of a DNA-damage response signature; and selecting one or more CRISPR-Cas systems that do not result in expression of a DNA-damage response signature.

DNA damage response signature guided rational design of CRISPR-based systems and therapies

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Boston, MA, United States of America

Rameen Beroukhim