Researchers engineer in vivo delivery system for prime editing, partially restoring vision in mice

Prime editing, a versatile form of gene editing that can correct most known disease-causing genetic mutations, now has a new vehicle to deliver its machinery into cells in living animals.

A team of researchers at the Broad Institute of MIT and Harvard has engineered virus-like particles to deliver prime editors to cells in mice at a high enough efficiency to rescue a genetic disorder. In the new work – published in Nature Biotechnology, the team adapted engineered virus-like particles (eVLPs) that they had previously designed to carry base editors another type of precision gene editor that makes single-letter changes in DNA.

The team used their new system to correct disease-causing mutations in the eyes of two mouse models of genetic blindness, partially restoring their vision. They also delivered prime editors to the mouse brain, and did not detect any off-target editing.

"This study represents the first time to our knowledge that delivery of protein-RNA complexes has been used to achieve therapeutic prime editing in an animal," said David Liu, senior author of the study and Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad. Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.

Image source: An et al. (2023), Nature Biotechnology.