Professor Virginijus Siksnys: A Treasure Trove of DNA Scissors: CRISPR-Cas and Beyond

IAS NTU Lee Kong Chian Distinguished Professor Public Lecture by Professor Virginijus Siksnys (Kavli Prize laureate in Nanoscience 2018).
Bacteriophages (viruses that infect bacteria) pose a lethal threat to bacteria. In order to survive the virus onslaught, bacteria built multiple defense barriers. In prokaryotes, restriction-modification system acts as an innate immune system of bacteria that destroys invading phage DNA. On the other hand, CRISPR-Cas system functions as an adaptive immune system that provides resistance against invading viruses. Deciphering the molecular mechanisms underlying the CRISPR-Cas immunity paved the way for the development of novel programmable DNA scissors for targeted genome engineering. CRISPR-Cas nucleases as exemplified by Cas9 and Cas12 are widely used for genome editing applications and are rapidly advancing into the clinics for the treatment of different diseases. However, delivery of Cas9 and Cas12 nucleases using AAV vectors is still a challenge, therefore smaller DNA scissors are highly desirable. Professor Virginijus Siksnys' team showed recently that transposon-associated TnpB protein is a very compact RNA-directed nuclease that cleaves dsDNA in the human cells, paving the way for the development of a new class non-CRISPR-Cas nucleases.