Abstract: Disclosed are polypeptides comprising two heterologous polypeptide domains, wherein the first polypeptide domain comprises a Cas protein and wherein the second polypeptide domain comprises a zinc finger protein 865 (ZNF865) or fragment thereof. Disclosed are polynucleotides capable of encoding a polypeptide comprising two heterologous polypeptide domains, wherein the first polypeptide domain comprises a Cas protein and wherein the second polypeptide domain comprises ZNF865 or fragment thereof. Disclosed are vectors comprising one or more of the polynucleotides. Disclosed are methods of using the disclosed polypeptides, polynucleotides and vectors.

Abstract: Disclosed herein are compositions and methods for treatment and prevention of low back pain. The compositions include vectors comprising nucleotide sequences encoding one or more CRISPR-Cas system guide RNAs and a RNA-directed nuclease. The methods include modulating expression of one or more genes in a cell using said compositions, introducing a CRISPR-Cas system into a cell comprising one or more vectors comprising said compositions, including site-specific DNA cleavage in a cell, and treating a subject having lower back pain, and lower back pain cause by degenerative disc disease using the compositions disclosed herein.