Researchers at the Broad Institute of MIT and Harvard have perfected a genome editing technology, now capable of inserting or replacing entire genes in human cells, paving the way for potential therapeutic applications.
Scientists in David Liu's lab have improved a gene editing system called eePASSIGE (prime-editing-assisted site-specific integrase gene editing), which can efficiently insert large DNA sequences into the genome of human cells. This advance could help develop universal gene therapies for diseases like cystic fibrosis, which is caused by many different mutations in a single gene.
The method combines prime editing, which can make DNA modifications up to about 200 base pairs, with newly developed recombinase enzymes that insert large DNA sequences of several thousand base pairs at specific locations in the genome. The eePASSIGE system, described in
Nature Biomedical Engineering, makes gene-sized modifications much more efficiently than other similar methods.
David Liu, a professor at Harvard and principal investigator of the study, stated: "To our knowledge, this is one of the first examples of programmable targeted gene integration in mammalian cells meeting key criteria for therapeutic relevance. At these efficiency levels, we hope that many loss-of-function genetic diseases could be alleviated or corrected if the efficiency observed in cultured human cells can be translated to the clinic."
Students Smriti Pandey and Daniel Gao, co-first authors of the study, collaborated with teams from Mark Osborn at the University of Minnesota and Elliot Chaikof at the Beth Israel Deaconess Medical Center. Smriti Pandey emphasized: "This system offers promising opportunities for cellular therapies where it can be used to precisely insert genes into cells outside the body before administering them to patients to treat diseases."
Daniel Gao added: "It's exciting to see the high efficiency and versatility of eePASSIGE, which could enable a new category of genomic medicines. We also hope it will be a tool that scientists in the research community can use to study fundamental biological questions."
David Liu and his team are continuing to develop this technology, seeking to combine it with delivery systems like virus-like particles (eVLPs) to overcome traditional obstacles to therapeutic gene editor delivery in the body.
Article author: Cédric DEPOND