Dissecting the mechanism of CRISPR–Cas technologies to design efficient biotechnologies

CRISPR–Cas enzymes have enabled us to manipulate the genetic code with unparalleled precision and efficiency. Here I explore the structural and biochemical intricacies that govern the functionality of CRISPR–Cas technologies, emphasizing the need for a nuanced mechanistic understanding to overcome current limitations and pave the way for safer and more effective genome-editing applications in medicine and research.

CRISPR–Cas enzymes have emerged as a molecular scalpel for scientists and physicians, who are now able to target and manipulate our genetic code efficiently and precisely. Over the past ten years, scientists have leveraged the ability of these enzymes to target specific genomic regions, beginning with cytosine and adenine base editors, and followed by prime and click editing technologies¹ that expanded editing to transversion mutations, insertions and deletions. CRISPR-based technologies have made detecting and treating disease, drug and genetic screening, and creating genetically modified crops more accessible than ever before.