Embodiments of the disclosure encompass methods and compositions for the treatment of medical conditions in which cell regeneration is in need, including neural cells. In specific embodiments, the cell are retinal cells and include Müller glial cells. In particular embodiments, an individual with retinal regeneration is provided an effective amount of one or more histone acetylase inhibitors for the purpose of regenerating retinal cells, including retinal neurons.

The present disclosure provides novel cancer therapies. The treatment of cancers harboring EP300 mutations with CREBBP inhibition therapy is described.

The present disclosure relates generally to methods and compositions for modulating frataxin (FXN) expression, e.g., to treat Friedreich ataxia (FRDA).

Single-module nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes activate and transform carboxylic acids in both primary and secondary metabolism; and are of great interest due to their biocatalytic potentials. The single-module NRPS IvoA is essential for fungal pigment biosynthesis. As disclosed herein, we show that IvoA catalyzes ATP-dependent unidirectional stereoinversion of L-tryptophan to D-tryptophan with complete conversion. While the stereoinversion is catalyzed by the epimerization (E) domain, the terminal condensation (C) domain stereoselectively hydrolyzes D-tryptophanyl-S-phosphopantetheine thioester and thus represents a noncanonical C domain function. Using IvoA, we demonstrate a biocatalytic stereoinversion/deracemization route to access a variety of substituted D-tryptophan analogs in high enantiomeric excess.

Provided herein are antisense oligonucleotides and prophylactic and therapeutic methods featuring such oligonucleotides. These oligonucleotides and methods are useful for treating or preventing ataxia telangiectasia in a subject. Specifically, the disclosure provides antisense nucleobase oligomers each comprising (8-40) nucleobases, wherein at least 90% of said nucleobases or more than (8) consecutive nucleobases of the oligomer are complementary to a nucleic acid sequence in an Ataxia-Telangiectasia Mutated (ATM) allele comprising a mutation associated with aberrant splicing.

Compositions and methods for assessing protein function are provided. A modified SpyCatcher protein that can include a tag is provided. Modified SpyCatcher proteins linked to a protein of interest, such as a nuclease are also provided. The methods include contacting a SpyCatcher protein and a SpyTagged protein to form a complex that may further include a protein of interest, one or more nucleic acids, and/or a nuclease. The methods can be used to purify a protein of interest or identify or target a protein binding site in a nucleic acid.

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.

Disclosed herein are CRISPR/Cas9-based gene activation systems that include a fusion protein of a Cas9 protein and a protein having histone acetyltransferase activity, and methods of using said systems.

The present invention relates to a polypeptide comprising a transposase and at least one heterologous chromatin reader element (CRE). Further, the present invention relates to a polynucleotide encoding the polypeptide. Furthermore, the present invention relates to a vector comprising the polynucleotide. In addition, the present invention relates to a kit comprising a transposase and at least one heterologous chromatin reader element (CRE).