Conjugates of guide RNA-Cas protein complex for genome and epigenome editing

Abstract

Provided herein are compositions of conjugates of a guide RNA(s)-CRISPR Cas protein (RNP) complex. The conjugate comprises a guide RNA(s)-CRISPR Cas protein (RNP) complex and one or more molecules selected from PEG, non-PEG polymers, ligands for cellular receptors, lipids, oligonucleotides, polysaccharides and peptides and chemically linked to the Cas protein and/or guide RNA(s). Also provided a guide RNA-DNA template conjugate comprises a DNA template with 5-methylcytosines at specific positions for epigenome editing by DNA methylation at a single nucleotide resolution level. The conjugates are delivered to targeted cells as RNP complexes, or formed in targeted cells from guide RNA conjugates and an mRNA or a viral vector encoding a Cas protein, or formed in targeted cells from a crRNA conjugate(s) and a viral vector encoding both a Cas protein and a tracrRNA. Also provided are preparation methods and uses of these conjugates.

Dependencies are inferred from the claim text.