Abstract:
This disclosure relates to the genetic modification of DNMT3A gene in immune cells. In certain embodiments, the modified immune cells may be used in adoptive T cells therapies to enhance immune responses against cancer or chronic infections. In certain embodiments, the disclosure relates to deleting, changing, or inserting nucleotides within the DNMT3A gene in immune cells, e.g., human CD8 T cells, such that the DNMT3A gene product does not function for methylation. In certain embodiments, modification of the DNMT3A gene provides an improvement in antigen-specific T cells functions and/or an enhancement of the longevity of the cells.
Abstract:
The present invention provides new methods of inhibiting aberrant DNA methyltransferase 3B (DNMT3B) transcripts containing abnormal splicing. Inhibitory nucleic acids, such as interfering RNAs and antisense molecules target improperly retained introns, thereby selectively inhibiting aberrant transcripts. Methods of treating cancers that involve aberrant DNMT3B transcripts also are provided.
Abstract:
Isolated cells genetically modified to express a DISRAM system are provided. Accordingly there is provided an isolated cell genetically modified to express a DISARM system having an anti-phage activity, the system comprising a drmM polypeptide; a drmA polypeptide; a drmB polypeptide; and a drmD polypeptide or a drmE polypeptide. Also provided are compositions and methods for conferring phage resistance to bacteria or for conferring bacterial susceptibility to phages.
Abstract:
A method for treating cancer in a subject in need thereof includes administering to cancer cells of the subject an agent effective to modulate the level of DNMT1-associated RNA and/or the interaction of DNMT1-associated RNA and DNMT1 in the cancer cells of the subject. Embodiments described herein relate to RNAs (e.g., IncRNAs) associated with DNA methyltransferase 1 (DNMTI-associcated RNA) in human cancer cells, methods and compositions of modulating the levels of DNMTI-associcated RNA and/or the interaction of DNMT1-associated RNA and DNMT1 in cancer cells of the subject to treat cancer cells or a subject in need thereof, and/or methods of measuring the expression profile of DNMT1 associcated RNA to determine whether the subject has cancer or an increased risk of cancer and/or the efficacy of a therapeutic regimen agent.
Abstract:
The present disclosure relates to methods of treating AML, associated with DNMT3A mutations by administering one or more DOT1L inhibitors or related pharmaceutical compositions to subjects in need thereof.
Abstract:
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.
Abstract:
This invention relates to compositions, methods, strategies, and treatment modalities related to the epigenetic modification of hepatitis B virus (HBV) genes.
Abstract:
Provided herein are gene repressor systems comprising fusion proteins, such as fusion proteins comprising a DNA binding domain such as a TALE, zinc finger or catalytically-dead CRISPR protein and guide nucleic acid (gRNA), which are useful in the repression of a proprotein convertase subtilisin kexin Type 9 (PCSK9) gene. Also provided are methods of using such systems to repress transcription of PCSK9.