The Cas9 nuclease causes double-stranded breaks at targeted gene sequences guided by a small guide RNA. The resulting DNA damage causes gene knockout when repaired via error-prone non-homologous end joining. Newer versions like Cas13 are RNA-guided and can directly cleave mRNAs instead of genomic DNA. Researchers can also engineer "dead" Cas9 lacking nuclease activity to bind genes and block their transcription through steric interference specifically.