Tuning CRISPR/Cas9 activity with chemically modified nucleotide substitutions

A composition comprising a Cas9 protein, a first oligonucleotide comprising a first region having a 5′ end and a 3′ end and a second region, and a second oligonucleotide comprising a first region and a second region, wherein said second region of said first oligonucleotide interacts with said first region of said second oligonucleotide, and said second region of said second oligonucleotide interacts with said Cas9 protein, wherein all nucleotides of said first oligonucleotide are 2′-deoxyribonucleotides or 2′-deoxyribonucleotide analogs.