Scientists restore vision in mice, achieve 170 fold gene editing boost

Scientists at MIT and Harvard found a better way to fix genetic mistakes. They have designed tiny, virus like particles to carry prime editors into mouse cells with a high success rate, effectively correcting a genetic disorder. Prime editing is a versatile editing technique capable of correcting disease causing genetic mutations.

By tweaking these engineered virus like particles (eVLPs) they improved the editing process by 170 times in human cells. In tests on mice with genetic eye problems, they corrected the mistakes and partially restored their vision. Promising treatment for genetic disorders Importantly, when they used the same method to edit genes in the mouse brain, there were no unintended changes.

This breakthrough suggests prime editing could be a promising treatment for genetic disorders in living animals. "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," David Liu, senior author of the study.

Scientists are exploring gene editing to fix genetic issues causing diseases. Prime editing, introduced in 2019, is a powerful method that allows precise and diverse changes in DNA. However, delivering this editing system into living animal cells is tricky. The system includes a Cas9 protein, an engineered guide RNA, and a reverse transcriptase.

Different methods, like lipid nanoparticles and viruses, have been used, with virus like particles (VLPs) showing promise. VLPs are made of viral proteins and carry cargo but don't contain viral material. Though VLPs have had modest success, they need specific engineering for each cargo type. Testing in mice model Liu and his team tested their system in mice to fix two different genetic problems in the eyes.

One issue causes a disease called retinitis pigmentosa, leading to gradual vision loss, and the other is linked to blindness in a condition called Leber congenital amaurosis (LCA) in humans. Using their eVLPs, they corrected the mutations in about 20 percent of the animals' retina cells, partially restoring their vision.

"We initially hoped that we could just take the eVLPs that we had painstakingly developed and optimized for base editing and apply them to prime editors," said Meirui An, first author of the study. "But when we tried that, we observed almost no prime editing at all." They enhanced how the prime editing cargo was packaged, separated from the delivery vehicle, and entered target cells' nuclei.

The coordinated improvements led to a 100 fold increase in efficiency, potentially making the technique suitable for therapeutic use in animals. "When we combined everything together, we saw improvements of roughly 100 fold compared to the eVLPs that we started with," said Liu. "That kind of improvement in efficiency should be enough to give us therapeutically relevant levels of prime editing, but we didn't know for sure until we tested it in animals." The was published today in ..