BOSTON — In a potentially significant advance for the genome editing field, researchers from the biotechnology company Caszyme and the Vilnius University Institute of Biotechnology in Lithuania have developed a potent and compact variant of Cas12l nuclease. Giedrius Gasiūnas, PhD, Caszyme co-founder and CEO, presented highlights of the research at ASGCT.
The work represents “a great example of the potential of continued mining for novel Cas effectors within the bacterial metagenomic diversity dark matter,” said Rodolphe Barrangou, PhD, Editor in Chief of The CRISPR Journal, which will shortly be publishing a paper on the Lithuanian team’s results. Barrangou emphasized the need for more diverse effectors to address the technical shortcomings of the CRISPR toolbox, highlighting the significance of this study.
The Lithuanian team, including veteran gene editor Virginijus Siksnys, PhD, utilized a hybrid approach to optimize Cas12l. By combining cryo-electron microscopy (cryo-EM) structure-guided design with artificial intelligence (AI) protein language models, they engineered a variant (Asp2Cas12l M82) that overcomes the known efficiency limitations of the Cas12l family. This advancement positions the M82 variant as a promising candidate for therapeutic applications, particularly given its compact size and improved editing efficiency compared to traditional Cas9.
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