Abstract: Provided are compositions and methods for altering gene expression in cells. The compositions and methods may utilize a nucleic acid sequence that has a genetically modified trans-activating crRNA (tracrRNA) sequence, where at least one uracil nucleotide of the tracrRNA sequence is replaced with a nucleotide other than uracil, and/or a nucleic acid sequence that has a guide RNA (gRNA) sequence wherein one or more cytosine nucleotides and/or one or more uracil nucleotides of said gRNA sequence are modified nucleotides. Also provided are methods of treating a disorder in a subject in need of the treatment. The method may involve administering to the subject the nucleic acid or a vector thereof in combination with an RNA-guided DNA endonuclease enzyme.

Abstract: The disclosure provides, inter alia, fusion proteins comprising a zinc finger domain and a transcriptional activator, nucleic acids, vectors, and exosomes that can be used to activate transcription in a cystic fibrosis transmembrane conductance regulator gene and treat cystic fibrosis.

Abstract: Provided are compositions and methods for activating latent Human Immunodeciency Virus (HIV). The compositions and methods may utilize a recombinant peptide that has a DNA-binding zinc finger domain specific to the HIV LTR sequence. The recombinant peptide may also have a transcription factor (e.g. a transcription activator) that is conjuated to the zinc finger domain. Also provided are methods of treating HIV in a subject in need of the treatment. The method may involve activation of latent HIV in cells of the subject and selectively removing such cells from the subject, providing complete and effective treatment of HIV.

Abstract: Provided are compositions and methods for activating latent Human Immunodeficiency Virus (HIV). The compositions and methods may utilize a recombinant peptide that has a DNA binding zinc finger domain specific to the HIV long terminal repeat (LTR) sequence. The recombinant peptide may also have a transcription factor (e.g. a transcription activator) that is conjugated to the zinc finger domain. Also provided are methods of treating HIV in a subject in need of the treatment. The method may involve activation of latent HIV in cells of the subject and selectively removing such cells from the subject, providing complete and effective treatment of HIV.

Abstract: Provided herein are, inter alia, compositions and methods for the treatment of hypercholesterolemia. The compositions include double-stranded and single-stranded RNAs capable of repressing IncRNA and concomitantly increasing LDLR activation. The compositions are useful for activating LDLR in liver cells.

Abstract: Provided herein are, inter alia, compositions and methods for the treatment of hypercholesterolemia. The compositions include double-stranded and single-stranded RNAs capable of repressing IncRNA and concomitantly increasing LDLR activation. The compositions are useful for activating LDLR in liver cells.

Abstract: Provided are compositions and methods for altering gene expression in cells. The compositions and methods may utilize a nucleic acid sequence that has a genetically modified trans-activating crRNA (tracrRNA) sequence, where at least one uracil nucleotide of the tracrRNA sequence is replaced with a nucleotide other than uracil, and/or a nucleic acid sequence that has a guide RNA (gRNA) sequence wherein one or more cytosine nucleotides and/or one or more uracil nucleotides of said gRNA sequence are modified nucleotides. Also provided are methods of treating a disorder in a subject in need of the treatment. The method may involve administering to the subject the nucleic acid or a vector thereof in combination with an RNA-guided DNA endonuclease enzyme.

Abstract: Provided are compositions and methods for activating latent Human Immunodeficiency Virus (HIV). The compositions and methods may utilize a recombinant peptide that has a DNA binding zinc finger domain specific to the HIV long terminal repeat (LTR) sequence. The recombinant peptide may also have a transcription factor (e.g. a transcription activator) that is conjugated to the zinc finger domain. Also provided are methods of treating HIV in a subject in need of the treatment. The method may involve activation of latent HIV in cells of the subject and selectively removing such cells from the subject, providing complete and effective treatment of HIV.

Abstract: Provided herein are, inter alia, compositions and methods for the treatment of hypercholesterolemia. The compositions include double-stranded and single-stranded RNAs capable of repressing IncRNA and concomitantly increasing LDLR activation. The compositions are useful for activating LDLR in liver cells.

Abstract: The present invention relates to transcriptional gene silencing (TGS) in mammalian, including human, cells that is mediated by small interfering RNA (siRNA) molecules. The present invention also relates to a double stranded nucleic acid that directs methylation of histones associated with target genes that produce low copy promoter-specific RNA. It has been found that siRNAs can be used to direct methylation of histones in mammalian, including human, cells.

Abstract: The present invention relates to transcriptional gene silencing (TGS) in mammalian, including human, cells that is mediated by small interfering RNA (siRNA) molecules. The present invention also relates to a double stranded nucleic acid that directs methylation of histones associated with target genes that produce low copy promoter-specific RNA. It has been found that siRNAs can be used to direct methylation of histones in mammalian, including human, cells.

Abstract: The invention is directed to compositions and methods for RNA-mediated gene regulation, e.g., transcription regulation, e.g., by transcriptional silencing of genes. In one aspect, the invention provides methods using siRNAs directed at a transcription regulator, e.g., a promoter or enhance sequence, of a gene target molecule. In one aspect, this results in in vivo DNA methylation and/or modification of associated chromatin (e.g., histone proteins) accompanied by and/or partial or complete transcription gene silencing in a cell, such as a mammalian cell, e.g., a human cell.