Modified guide rna for reducing off-target editing

A synthetic guide RNA comprising:

• (i) a first nucleotide sequence comprising at least one modified nucleotide, wherein the first nucleotide is partially or completely complementary to a target nucleic acid;
• and
• (ii) a second nucleic acid sequence which interacts with a CRISPR-associated protein (Cas) polypeptide,
• wherein the synthetic guide RNA guides the Cas polypeptide to the target nucleic acid, and wherein the synthetic guide RNA exhibits a reduced off-target effect and/or enhanced on-target editing activity, relative to an unmodified gRNA.