Azide-functionalized SpCas9 enables generation of site-selective and bioactive Cas9-siRNA conjugates

Key Points

• The research aims to create a new method for site-specific gene editing using a modified Cas9 enzyme for drug delivery.
• Cas9 was engineered for regioselective azide-alkyne click conjugation.
• Functionalized siRNA was utilized to test conjugation efficiency and bioactivity.
• Proof of concept was established by assessing therapeutic efficacy of the conjugates.
• The azide-functionalized SpCas9 successfully conjugated to siRNA.
• Conjugates showed enhanced therapeutic activity compared to traditional delivery methods.
• Significant increases in target gene knockdown were observed with the new approach.