Using programmable dna binding proteins to enhance targeted genome modification

A method for increasing targeted genome modification efficiency and/or specificity in a eukaryotic cell, the method comprising introducing into the eukaryotic cell:

• (a) a programmable DNA modification protein or nucleic acid encoding the programmable DNA modification protein, wherein the programmable DNA modification protein is a RNA-guided clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated (Cas) (CRISPR/Cas) nuclease system or the programmable DNA modification protein is a fusion protein comprising a catalytically inactive CRISPR/Cas system linked to a non-nuclease domain;
• and
• (b) at least one programmable DNA-binding protein or nucleic acid encoding the at least one programmable DNA-binding protein, wherein the at least one programmable DNA-binding protein is a CRISPR/Cas system lacking nuclease activity,
• wherein each CRISPR/Cas system comprises a CRISPR/Cas protein and a guide RNA,
• wherein the programmable DNA modification protein is targeted to a target chromosomal sequence and each of the at least one programmable DNA-binding protein is targeted to a site proximal to the target chromosomal sequence, and
• wherein binding of the at least one programmable DNA-binding protein to the site proximal to the target chromosomal sequence increases accessibility of the programmable DNA modification protein to the target chromosomal sequence, thereby increasing targeted genome modification efficiency and/or specificity.