A novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-based technology developed by Script Biosciences can correct mutations causing Duchenne muscular dystrophy (DMD) and cystic fibrosis (CF) with high efficiency and low on-target DNA damage rate, according to a study presented at the 25th American Society of Gene and Cell Therapy (ASGCT) Annual Meeting.

According to the company, the new technology, called CasPlus, “provides a safer and more efficient next-generation gene-editing approach.”

Using cells grown in culture, researchers showed that CasPlus successfully restored the reading frame of the DMD gene that had mutations in exons 51 and 53 and rescued the expression of the dystrophin protein. Similarly, they showed that CasPlus could correct the F508del mutation in the CFTR gene causing most cases of CF.


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“We are encouraged by this data and it is a step forward in our mission to develop lasting cures for patients suffering from serious diseases,” Anil Namboodiripad, PhD, the chief executive officer of Script Biosciences, said in a press release. “In vivo translational studies in humanized mouse models are ongoing.”

Read more about the etiologies of DMD and CF

CasPlus is a novel CRISPR/Cas-based technology that uses a DNA polymerase to allow the exogenous template-free DNA repair of double-strand breaks induced by Cas9 with high efficiency. It prevents the formation of large on-target DNA deletions and rearrangements, which is one of the major safety concerns in first-generation CRISPR/Cas9 gene-editing systems.

“While numerous approaches have already been developed to reduce well-known off-target effects of CRISPR-mediated editing, the CasPlus system prevents CRISPR-mediated collateral on-target large deletions and thus offers the promise of safer therapeutic gene editing in humans,” said Chengzu Long, PhD, principal investigator and assistant professor in the Division of Cardiology and the Helen and Martin Kimmel Center for Stem Cell Biology at New York University’s Grossman School of Medicine in New York City.

“We plan to advance our lead program in DMD towards [investigational new drug]-enabling studies, while also expanding our pipeline to other gene targets,” Dr. Namboodiripad added.

The ASGCT annual meeting was held in Washington, DC, in May.

Reference

The CasPlus gene editing platform technology can correct mutations associated with Duchenne’s muscular dystrophy and cystic fibrosis with high efficiency and exceptionally low rates of on-target DNA damages. News release. Script Biosciences Inc; May 17, 2022.