Abstract:
Methods for reactivating genes on the inactive X chromosome that include administering one or both of a DNA methyltransferase (DNMT) Inhibitor and/or a topoisomerase inhibitor, e.g., etoposide and/or 5′-azacytidine (aza), optionally in combination with an inhibitor of XIST RNA and/or an Xist-interacting protein, e.g., a chromatin-modifying protein, e.g., a small molecule or an inhibitory nucleic acid (such as a small inhibitory RNA (siRNAs) or antisense oligonucleotide (ASO)) that targets XIST RNA and/or a gene encoding an Xist-interacting protein, e.g., a chromatin-modifying protein.
Abstract:
The disclosure provides constructs comprising a first fusion protein, a second fusion protein, and a linker, wherein the first fusion protein and the second fusion protein each include an affinity reagent and a reactive enzyme, and the linker includes a first and second functional groups specific for irreversibly inhibiting the first and second fusion protein reactive enzymes. The disclosure further provides a method including (a) contacting a first fusion protein including an affinity reagent and a reactive enzyme with a linker including a functional group specific for irreversibly inhibiting the first fusion protein reactive enzyme thereby coupling the first fusion protein and the linker, and (b) contacting a second fusion protein including an affinity reagent and a reactive enzyme with the linker, the linker including a functional group specific for irreversibly inhibiting the second fusion protein reactive enzyme thereby coupling the second fusion protein and the linker.
Abstract:
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.
Abstract:
An epigenetic silencer factor (ESF) comprising a transcription factor DNA-binding domain operably linked to at least one epigenetic effector domain, wherein the transcription factor is an oncogenic transcription factor or a cancer-associated transcription factor.
Abstract:
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).
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:
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.
Abstract:
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.
Abstract:
The present invention provides a promoter of differentiation from a hepatic progenitor cell into a hepatocyte, which contains a substance that suppresses expression of Dnmt-1 or a substance that inhibits the function of Dnmt-1 as an active ingredient, and a method of producing a hepatocyte (preferably hepatocyte with high maturity) from a hepatic progenitor cell.