Described herein are compositions, systems, and methods for modulating gene expression. Also described herein are systems and methods for treating a disease or a condition by modulating gene expression. In some embodiments, the compositions, systems, and methods provided herein are used to treat familial hypercholesterolemia. In some embodiments, the compositions, systems, and methods provided herein involve suppression of endogenous PCSK9.

The present disclosure provides compositions with a modulating gene expression and methods for modulating transcription.

The present disclosure provides compositions with a modulating gene expression and methods for modulating transcription.

BrecOFF is an epigenome editor that specifically targets the HIV promoter, long tandem repeat (LTR), to deposit DNA and histone repressive markers and thereby silencing its transcription and reactivation. BrecOFF comprises of 3 modules (FIG. 1a). The DNMT3A and cofactor DNMT3L are the de novo DNA methylation machinery that marks DNA with repressive methylation marks. The Krppel associated box (KRAB) domain is a transcriptional repression domain by recruit of TRIM28 repression complex and addition of repressive epigenetic marks on histones. Finally, dBrec1 is a catalytically inactive version of Brec1, a Cre-based directly evolved recombinase that specifically recognizes the R region of the HIV LTR without off-target effects

Provided herein is a method of detecting the presence or absence of a single naturally- or synthetically-modified nucleobase in a polynucleotide molecule, which is achieved by first contacting the polynucleotide molecule with one or more reagents capable of attaching a detectable moiety to at least one nucleobase of the polynucleotide molecule or to a nucleobase adjacent to the modified nucleobase, thereby forming a labeled nucleobase, while the presence or absence of the modified nucleobase is determined by the attachment. The polynucleotide molecule is then assayed using a nanopore device to detection the presence or absence of the labeled nucleobase, wherein the detectable moiety attached to at least one nucleobase in the polynucleotide molecule has a molecular weight that ranges from 40 to 1,000 Daltons, and the average pore diameter in the nanopore device is no more than 5 nanometers.

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

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.

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.

The present application relates to the field of biomedicine, and provides an epigenetic editing tool for targeting a hepatitis B virus gene and a use thereof.