CRISPR pioneer helps create gene-editing delivery system

CRISPR pioneer Feng Zhang, Ph.D., and his colleagues have come up with a new way to get gene editing and other molecular therapeutics to target cells. The approach uses a protein found naturally in humans, potentially avoiding the immune attacks that prevent repeat dosing using viral vectors. 

The research, details of which were published in Science, focuses on PEG10, a protein that binds to its own mRNA in the human body and forms a protective shell around the nucleic acid. Another human protein, ARC, was shown to form similar structures several years ago, but the drug delivery potential of the molecules has gone untapped to date. 

Zhang and his colleagues including Michael Segel and Blake Lash, the first and second authors of the paper, set out to unlock the drug delivery potential of PEG10 by engineering the protein. By looking into the molecular sequences that PEG10 uses to recognize and package its mRNA, the researchers engineered the protein to encapsulate other nucleic acids. 

Finally, the team added proteins to enable the targeted delivery of the payload using SEND, an acronym for selective endogenous encapsidation for cellular delivery. “By mixing and matching different components in the SEND system, we believe that it will provide a modular platform for developing therapeutics for different diseases,” Zhang told MIT News.

The endogenous nature of PEG10 could give it an advantage over other delivery vehicles. While the immune system recognizes viral vectors as foreign and mounts an attack, PEG10 may enter the body without setting off any alarms. That prospect remains unproven but, if further research shows it to be true, PEG10 could enable the repeat delivery of gene therapies with minimal side effects.

Other groups are trying to achieve the same outcome using different means. Multiple groups are working on exosomes and others, such as Fierce 15 winner Carmine Therapeutics, are developing twists on the concept.