The present invention relates to compositions and methods for the inhibition of the infectivity of a herpesvirus. In certain embodiments, the compositions and methods provide a CRISPR-associated peptide and a guide nucleic acid, which induce the mutation of herpesvirus genome, thereby inhibiting the infectivity of the herpesvirus. Further disclosed are Cas peptides including Cas9 or a variant thereof comprising one or more point mutations relative to wildtype Streptococcus pyogenes Cas 9 (spCas9), and Cpf1 or a variant thereof.

Provided are compositions and methods for inducing expression of human beta-globin in erythrocytes for use in prophylaxis and/or therapy of a hemoglobinopathy in an individual. The method generally entails introducing into CD34+ cells a polynucleotide encoding: i) a 5′ long terminal repeat (LTR) and a self-inactivating 3′ LTR; ii) at least one polyadenylation signal; iii) at least one promoter; iv) a globin gene locus control region (LCR); v) an ankyrin insulator element (Ank); vi) a Woodchuck Post-Regulatory Element (WPRE) configured such that the WPRE does not integrate into a target genome; and vii) a sequence that is a reverse complement of a sequence encoding human beta-globin, and can include beta-globin that has a PT87Q mutation. Intron 2 of the beta globin gene can be a complete intron. Modified erythrocyte progenitor cells, recombinant vectors and virions comprising recombinant polynucleotides, and methods of making the vectors and virions are included.

This invention relates to the treatment of cancer in an individual by administration of a population of modified T cells that express a recombinant cAMP phosphodiesterase (PDE) or a fragment thereof and an antigen receptor which binds specifically to cancer cells in the individual. Populations of modified T cells and methods of producing populations of modified T cells are provided, along with pharmaceutical compositions and methods of treatment

The present disclosure provides methods and systems for identification of genomic regions for therapeutic targeting. A method for identifying one or more genomic regions for therapeutic targeting, which may facilitate re-programming of a cell from one phenotypic state to another, may comprise: providing single-cell RNA-seq data for a plurality of diseased cells and a plurality of normal cells of a cell type; mapping the single-cell RNA-seq data for the plurality of diseased cells and the plurality of normal cells into a latent space corresponding to a plurality of phenotypic states of the cell type; identifying, based at least in part on a topology of the latent space, the one or more genomic regions for therapeutic targeting; and electronically outputting the one or more genomic regions for therapeutic targeting.

Described herein are compositions and methods for treating Alzheimer's disease or dementia. The compositions include mammalian suppressor of taupathy 2 inhibitors (MSUT2). The MSUT2 inhibitors can be small interfering RNAs, guide RNAs, or small molecules. The methods include reducing accumulation of phosphorylated and aggregated human tau.

An invention provides a chimeric antigen receptor. The chimeric antigen receptor includes an extracellular domain including a heavy chain variable region, a light chain variable region of a single chain antibody fragment and CD8 hinge region; a transmembrane domain including an immune co-stimulator transmembrane domain; and an intracellular domain including an immune co-stimulator intracellular segment and CD3ζ chain. According to the embodiments of the invention, the chimeric antigen receptor can specifically recognize the tumor cells expressing the specific antigen and achieve the specific killing effect against the tumor cells expressing the high specific antigen.

In alternative embodiments, provided are compositions, including recombinant expression systems and vectors, products of manufacture and kits, and methods, for remotely-controlled and non-invasive manipulation of intracellular nucleic acid expression, genetic processes, function and activity in live cells such as T cells in vivo, for example, activating, adding functions or changing or adding specificities for immune cells, for monitoring physiologic processes, for the correction of pathological processes and for the control of therapeutic outcomes. In alternative embodiments, provided are blue-light-mediated light-inducible nuclear translocation and dimerization (LINTAD) systems for gene regulation to control cell activation based on the integration of light-sensitive LOV2-based nuclear localization, light-induced active transportation via the biLINuS motif, and CRY2-CIB1 dimerization that feature high spatiotemporal control to control or alter cell activities in vivo, for example, to limit CAR T cell activity to the tumor site for immunotherapy applications.

Provided is application of chimeric antigen receptor (CAR)-modified T (CART) cells in preparing drugs for cancer treatment, the CART cells contain an artificially-introduced costimulatory signal transduction domain, and the CART cell does not contain an artificially-introduced first signal transduction domain.

The present invention relates to a chimeric costimulatory antigen receptor (CoStAR) useful in adoptive cell therapy (ACT), and cells comprising the CoStAR. The CoStAR can act as a modulator of cellular activity enhancing responses to defined antigens. The present invention also provides CoStAR proteins, nucleic acids encoding the CoStAR and therapeutic uses thereof.

Various methods and compositions for treating age-associated conditions and other medical conditions, such as muscle diseases, type 2 diabetes, and/or obesity are described. Methods of enhancing cellular uptake of NMN and stimulating NAD+ production are further described. Various mammalian cells and mammalian cell lines are described including those comprising a cDNA encoding a Slc12a8 protein. Gene therapy vectors comprising a nucleic acid encoding Slc12a8 and non-human animals comprising an inactivating mutation in a Slc12a8 gene are also disclosed. Also described are methods for screening a candidate compound to identify compounds that promote NMN transport.