Described herein are compositions and methods for enhancing erythropoiesis in an individual in need thereof. Specifically agents that decrease the expression of Exosc10, such as inhibitory nucleic acid molecules, produce an increase in red blood cell production in the individual.

The invention involves inducing 3-50 or more mutations (e.g., any whole number between 3 and 50 of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such as AAV, and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model genetic disease, e.g. cancer. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., cancer.

A method of producing induced exosomes, the method comprising: contacting an isolated population of stem cells with an amount of a prostaglandin E receptor 4 (EP4) antagonist effective for inducing release of exosomes, whereby induced exosomes are released from the stem cells, and isolating the induced exosomes.

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.

A photocaged DNA nano-tweezer and methods of using said photocaged DNA nano-tweezer are described. In particular, provided herein is a DNA nano-tweezer comprising a hairpin with a single-stranded loop that comprises a first arm and a second arm; and a trigger strand complementary to the single-stranded loop and comprising at least one photocaged residue with a protecting group.

The present invention relates to the combination of a Dbait molecule with a KRAS inhibitor for treating cancer.

The present invention relates to a method for treating ocular disease in a subject in need thereof comprising a step of administering to said subject a therapeutically amount of an inhibitor of SOX21 gene expression and/or activity. By studying a mouse model of congenital microcoria, the inventors demonstrate that this ultra-rare and purely ocular disease is due to unanticipated complex mechanisms linked with 3D regulation of gene expression. They propose that the disease is due to the illegitimate expression of a transcription factor, SOX21, induced by the adoption of a DCT enhancer(s). They show that SOX21 binds to a regulatory region of the Tgfβ2 gene and the inventors demonstrate overexpression of this trophic factor in the iris and accumulation of its product in the aqueous humor of the mouse carrying the minimal MCOR deletion which recapitulates the observed accumulation in patients with POAG and one of our patient with MCOR.

A modified immune cell that has attenuated expression and/or activity of YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), and enhanced anti-tumor activity. A composition for stimulating T cell-mediated immune response to a cancer cell and/or a tumor antigen, including an agent capable of attenuating the expression and/or activity of YTHDF2, and a pharmaceutically acceptable excipient. A composition for treating cancer, comprising an agent capable of attenuating the expression and/or activity of YTHDF2. A method for activating an immune cell. A method for generating an immune cell. A method for treating a disease, disorder or condition associated with an expression of a tumor antigen in a subject in need thereof. A method for stimulating a T cell-mediated immune response to a cancer cell and/or a tumor antigen in a subject in need thereof.

Provided herein are nucleic acids useful as guide nucleic acids (gNAs), e.g., guide ribonucleic acids (gRNAs), in a CRISPR system wherein the guide nucleic acids contain one or more modifications to one or more nucleotides, use of such guide nucleic acids in modifying cells, and other uses wherein CRISPR Cas proteins are utilized.

Embodiments of the disclosure encompass systems, methods, and compositions related to selective advantages to somatic cells that harbor one or more particular genetic modifications. In particular embodiments, there is selective expansion of gene-targeted cells wherein the strategy involves deletion of an essential gene product that is replaced with targeted integration that also includes integration of a therapeutic transgene. The cells that harbor the replaced essential gene product, and thereby the therapeutic transgene, are selected for using pharmaceutical or nutritional agents that are linked to the function of the essential gene product.