Cas12l nucleases act like molecular scissors, making staggered cuts in DNA for precise genome editing.
CRISPR-Cas gene editing has transformed research and industry, enabling precise genome modification for diverse applications, including therapeutic development. However, this method is not without limitations. Many Cas nucleases, including the widely used Cas9 proteins, are large, difficult to deliver, and can introduce errors. Additionally, commercial licenses for Cas proteins are often prohibitively expensive.
In search of next-generation nucleases, the European gene editing company Caszyme discovered a new family of CRISPR-associated proteins, Cas12l nucleases. Approximately 850 amino acids in size, these compact proteins allow scientists to use delivery methods that were previously difficult with larger nucleases. Cas12l recognizes a cytosine-rich protospacer adjacent motif and generates staggered double-strand breaks in DNA, contributing to its typically higher efficacy compared to popular Cas proteins. “[Cas12l nucleases] achieve up to 100 percent editing efficiency when the market standard is around 50 percent,” said Monika Paulė, cofounder and chief executive officer of Caszyme, which offers licensing opportunities to researchers and companies. Consequently, Cas12l is an accessible, flexible, and proficient tool for therapeutic editing.
Cas12l’s compact design supports various delivery strategies while maintaining high editing efficiency for advanced therapeutic development.
Tomas Urbaitis, Caszyme
“Although [Cas12l is] relatively novel and maybe not as well-known and widely used as other nucleases, it is performing as good as or even better,” said Avencia Sanchez-Mejias, cofounder and chief executive officer of Integra Therapeutics, a Barcelona-based biotechnology company that uses the Cas12l nuclease in their gene writing platform. “It has been a pivotal point for us to get commercial access to a nuclease that allows us to deploy our technology.” Currently, the company is leveraging this platform to develop next-generation cell and gene therapies for the treatment of genetic diseases, cancer, and autoimmune disorders.
By offering this unique nuclease, Caszyme hopes that they can drive innovation across the global gene editing market, bring life-changing therapies to more patients, and highlight their home country’s role as a leader in this growing field. “We as a company come from Lithuania, and it is a country really having a great gene editing [and] molecular biology ecosystem,” said Paulė. “From the nomenclature, we got the letter L for our Cas12, but L also stands for Lithuania. So, we are proud of having a very unique tool from a really fast-growing country, which plays an important role in this CRISPR gene editing space.”
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