A product comprising two or more artificial transcription repressors (ATRs), or polynucleotides encoding therefor, selected from groups (a), (b), (c) or (d): (a) an ATR comprising a DNA-binding domain operably linked to a KRAB domain or homologue thereof; (b) an ATR comprising a DNA-binding domain operably linked to a DNMT3A, DNMT3B or DNMT1 domain or homologue thereof; (c) an ATR comprising a DNA-binding domain operably linked to a DNMT3L domain or homologue thereof; and (d) an ATR comprising a DNA-binding domain operably linked to a SETDB1 domain or homologue thereof, wherein at least two of the ATRs are selected from different groups (a), (b), (c) or (d).

This invention relates to compositions, methods, strategies, and treatment modalities related to the epigenetic modification of hepatitis B virus (HBV) genes.

This invention relates to compositions, methods, strategies, and treatment modalities related to the epigenetic modification of hepatitis B virus (HBV) genes.

Treatment and prevention of DNMT3A deficiency-associated diseases are provided. Compositions for treatment or prevention include at least one cDNA vector and/or at least one therapeutic agent capable of restoring DNMT3L activity, restoring DNMT3L expression, increasing DNMT3L activity, increasing DNMT3L expression, and/or increasing DNMT3A enzymatic activity. Methods for treatment or prevention include administering to a subject a composition including the at least one cDNA vector and/or at least one therapeutic agent. Methods of increasing DNMT3A activity in a subject having a DNMT3A mutation, methods of reversing a hypomethylation phenotype in bone marrow cells of a subject having a DNMT3A mutation, and methods of promoting cancer cell death in a subject having Acute Myeloid Leukemia (AML) are also provided.

The application provides modified immune effector cells wherein the DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mediated de novo DNA methylation of the cell genome is inhibited, and IL10 signaling pathway is enhanced. The application also provides related pharmaceutical compositions and the methods for generating such modified immune effector cells. The application further provides uses of such modified immune effector cells for treating diseases such as cancers, infectious diseases and autoimmune diseases.

Reduced genome bacteria with improved genetic stability are provided. Also provided are methods of producing polypeptides using the reduced genome bacteria with improved genetic stability.

This disclosure provides CRISPR/Cas9 based fusion molecules and guide RNAs for use in in vivo targeted reduction or elimination of VEGFA gene products. This disclosure also relates to formulations, methods of production and methods of use thereof.

This disclosure provides CRISPR/Cas9 based fusion molecules and guide RNAs for use in in vivo targeted reduction or elimination of PCSK9 gene products. This disclosure also relates to formulations, methods of production and methods of use thereof.

The invention relates to methods of modifying DNA methylation by contacting a cell with a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity and one or more guide sequences.

The disclosure provides, in various embodiments, fusion proteins comprising a DNA-binding domain, a DNMT3A-binding domain, and a H3K4me0; and polynucleotides and vectors encoding one or more of the fusion proteins. The disclosure also provides, in various embodiments, gene-delivery systems, cells, compositions (e.g., pharmaceutical compositions) and kits comprising one or more of the fusion proteins polynucleotides, or vectors; methods of epigenetically modifying a genomic locus in a cell; and methods of treating a subject (e.g., a human) in need thereof.