Abstract: Methods and products are described herein for the modification of nucleic acids using a CRISPR/Cas9 system. Also described herein are uses of such methods and products for the modification of a target nucleic acid in a cell, in vitro or in vivo. Such methods and products may also be used for prevention or treatment of a condition associated with a target polynucleotide.

Abstract: Described herein are reagents, products, methods, and uses thereof for modifying the genome of a cell at a MTOR locus, for example by nuclease-based (e.g. CRISPR/Cas9) modification. The modifications include a MTOR modification which confers resistance to an mTOR inhibitor. The modifications may further include a modification to introduce a nucleic acid or gene of interest. Introducing both modifications at the MTOR locus is an efficient and advantageous strategy which allows for targeted modification of both aspects (resistance and gene of interest) at the same locus, and further allows for the use of an mTOR inhibitor to select and enrich for such modified cells. Such modified cells may be used for a variety of applications, including therapeutic applications.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Lymphocytes having a suppressed autophagy gene useful in immunotherapy are disclosed. The lymphocytes can express an antigen targeting receptor such as a chimeric antigen receptor (CAR) or endogenous or engineered T-cell receptor to target cells expressing a tumor-specific antigen. Methods of making and using such lymphocytes are disclosed. Some such lymphocytes are useful in conducting CAR-T or TCR-T therapy.

Abstract: Methods and products are described herein for the modification of nucleic acids using a CRISPR/Cas9 system. Also described herein are uses of such methods and products for the modification of a target nucleic acid in a cell, in vitro or in vivo. Such methods and products may also be used for prevention or treatment of a condition associated with a target polynucleotide.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are homozygously modified organisms and methods of making and using these organisms.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are homozygously modified organisms and methods of making and using these organisms.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are methods and compositions for rapidly identifying and ranking nucleases for specific cleavage of a target sequence.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: Disclosed herein are methods and compositions for rapidly identifying active nucleases and cells having nuclease-mediated genomic modifications.