The present invention relates to genes coding for nucleases, processes for characterizing the nucleases, cells comprising the nucleases, and methods of using the nucleases.

Embodiments of the disclosure encompass methods and compositions for producing engineered mesenchymal stem/stromal cells (MSCs). The disclosure concerns large-scale processes for producing MSCs that are engineered to have disruption of expression of one or more genes using CRISPR and also express at least one heterologous antigen receptor. Specific embodiments include particular parameters for the process.

Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and non-LTR retrotransposon elements.

A group of gRNAs is provided, and the group of gRNAs comprises a first gRNA molecule; and a second gRNA molecule capable of defining a region in a genome sequence with the first gRNA molecule, wherein the region in the genome comprises a target sequence in need of removal.

Provided are methods, compositions, and cells for use in adoptive cell therapy for the treatment of cancer. The methods involve administering an effective amount of cells to a subject, wherein the cells are modified ex vivo to suppress endogenous Zbtb20 expression and/or activity within the modified cells. The cells may comprise a dominant negative Zbtb20 capable of suppressing endogenous Zbtb20 activity, at least one shRNA capable of suppressing endogenous Zbtb20 expression, or at least one sgRNA capable of suppressing endogenous Zbtb20 expression. The cells may further comprise an exogenous TCR and/or CAR suitable for treating cancer. The method can further involve administering one or more additional cancer therapies, such as cells which express at least one exogenous TCR and/or CAR suitable for treating cancer. The method can provide various advantages, such as a reduction and/or elimination of an amount of cancer cells in the subject.

Methods and compositions for producing fetal hemoglobin and treating a hemoglobinopathy or thalassemia are disclosed.

Compositions and methods are provided for production of cells useful in regenerative therapies.

Embodiments of the disclosure encompass improvements on cell therapies by allowing the cells to be more effective for cancer treatment, including in a solid tumor microenvironment. In specific cases, the cells are modified to have reduced or inhibited levels of expression of T-Cell Death Associated Gene 8 (TDAG8), such as by CRISPR gene editing. In specific cases, the cells are further modified to express, for example, one or more engineered receptors, one or more cytokines, and optionally a suicide gene.

The present disclosure provides compositions, methods, and systems related to genome editing technology. In particular, the present disclosure provides a novel CRISPR-based genome editing technology that involves the generation of abasic sites to facilitate genetic recombination, without the need for breaks in the DNA. The compositions, methods, and systems described herein address many of the drawbacks of currently available approaches, including off-target effects and cellular toxicity.

The present disclosure provides methods of treating subjects having psoriasis, and methods of identifying subjects having an increased risk of developing psoriasis.