eePASSIGE Engineers Gene-Sized Edits in Human Cells

By Katherine Li/May 16, 2024

The Broad Institute of MIT, Harvard University, and Howard Hughes Medical Institute (HHMI) scientists have created a new version of a crucial  editing technology that is able to replace whole genes in human cells. This new version, eePASSIGE, is able to effectively insert longer DNA sequences into the human cell at a much faster pace. 

The newly edited version of the editing technology utilizes and brings together prime editing as well as new recombinase enzymes in order to be able to quickly insert longer DNA sequences into the human cell genome. Scientists at the Liu lab reports that “the system makes gene-sized edits several times more efficiently than similar methods,” indicating the greater level of efficiency that this new technology is able to reach. The Liu lab focuses their research and design process on the new editing technology, using combinations of several different techniques in order to formulate a more efficient and productive one. 

Due to the effectiveness and capability of the improved version, there are several crucial potential therapeutic applications of prime editing. A professor at Harvard University who is a senior author of the study, Liu, states that “at these efficiencies, we expect that many if not most loss-of-function genetic diseases could be ameliorated or rescued, if the efficiency we observe in cultured human cells can be translated into a clinical setting.” This method is able to edit a fraction of the cells, allowing for it to potentially treat several genetic diseases; however, diseases that result as a loss of functional genes may not fare as well. 

Liu and his colleagues used a tool called PACE (phage-assisted continuous evolution) in order to develop better versions of the recombinase enzyme Bxb1---this enzyme was the main building factor of eePASSIGE. Liu’s study on integrating gene-sized cargo into mouse and human cells reported that four times more cargo was able to be integrated compared to its predecessor, PASSIGE. The results of this study prove to be a breakthrough in the field of genomic medicines, as the system provides potential long term benefits of discovering and developing further efficient ways of gene integration, allowing for more and more ways to treat certain genetic diseases that have never been seen before. 

Citations: 

Staff, G. (2024, June 11). EEPASSIGE engineers gene-sized edits in human cells . https://www.genengnews.com/topics/genome-editing/eepassige-engineers-gene-sized-edits-in-human-cells/