The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present disclosure provides methods and pharmaceutical compositions for treating or slowing the progression of cancer, i.e., pancreatic cancer or esophageal cancer, by administering to a human subject in need thereof a therapeutically effective amount of an inhibitor of the histone methyltransferase, SETD2.

The invention provides compositions and methods for generating improved T cells having increased Ezh2 activity and methods of use thereof in the treatment of cancer and chronic infection.

Disclosed are methods for treating Set1/COMPASS-associated cancers characterized by expression of Set1B/COMPASS. The methods typically include administering a therapeutic amount of an inhibitor of the Set1B/COMPASS pathway and/or an agonist for a target that is negatively regulated by the Set1B/COMPASS pathway.

The present invention provides methods and compositions to improve the efficiency of somatic cell nuclear transfer (SCNT) of human cells and the consequent production of human nuclear transfer ESC (hNT-ESCs). More specifically, the present invention relates to the discovery that trimethylation of Histone H3-Lysine 9 (H3K9me3) in reprogramming resistant regions (RRRs) in the nuclear genetic material of human donor somatic cells prevents efficient human somatic cell nuclear reprogramming or SCNT. The present invention provide methods and compositions to decrease H3K9me3 in methods to improve efficacy of hSCNT by exogenous or overexpression of the demethylase KDM4 family and/or inhibiting methylation of H3K9me3 by inhibiting the histone methyltransferases SUV39h1 and/or SUV39h2.

Engineered CRISPR-Cas9 nucleases with improved specificity and their use in genomic engineering, epigenomic engineering, genome targeting, and genome editing.

In some embodiments, methods of detecting an association between a query protein and a target moiety are described. In some embodiments, compositions are described. In some embodiments, kits are described.

Engineered CRISPR-Cas9 nucleases with improved specificity and their use in genomic engineering, epigenomic engineering, genome targeting, and genome editing.

Disclosed herein are methods and compositions for identifying transcriptional and epigenetic age-related markers. Disclosed herein are also methods and compositions for reprogramming cell age by modulating transcriptional and epigenetic age-related markers identified herein. The identified transcriptional and epigenetic age-related markers can also be used for measuring cellular age in a cell or tissue.

Provided herein are compositions and methods for improving immune system function. In particular, provided herein are compositions, methods, and uses of YY1 and EZH2 inhibitors for preventing and reversing T-cell exhaustion (e.g., for use in immunotherapy).