Gene therapy that restored sight in mice enters human glaucoma trial

The therapy stems from experiments Lu performed while earning his PhD at Harvard Medical School. In 2018, he used a cellular reprogramming technique to repair the crushed optic nerves of blinded mice, injecting the cells with a gene therapy designed to return them to a youthful state. Sixteen days later, the nerves were growing back, their axons appearing through a microscope as spidery orange filaments. Tests using rotating bars of light showed the mice were tracking changes in their surroundings; they could see again. Lu’s results were published in Nature in 2020.

ER-100 uses a shortened form of reprogramming. In 2006, Japanese researchers had shown that adding four genes, known by the acronym OSKM, could return adult cells to an embryo-like state. Lu removed Myc, the gene most likely to cause dangerous changes such as cancer, leaving three genes, OSK. Sinclair said Lu once texted him microscope images and asked, “What do you see here?” Sinclair answered, “I see the future.” Of the human trial, Sinclair said: “It’s remarkable that what he developed as a student is now going into humans. It’s barely even changed since he built it.”

Lu, 34, spoke to MIT Technology Review outside the Whitehead Institute in Cambridge, Massachusetts. He told the magazine that a great-aunt in China was killed crossing a road because she could not see oncoming traffic, and that his own genetic test had found a mutation for macular degeneration, a leading cause of vision loss in old age. Because bright sunlight is another risk factor, he wears dark glasses. “They protect me,” he said. “Plus, they look cool.” He described the eye as “a really unique system to study aging and rejuvenation.”

MIT Technology Review said the announcement had been big news, with a New York Times headline suggesting the technology could “change humanity” and one post on X declaring that “the fountain of youth is here.” Lu, however, has stayed out of the public discussion while working in the lab on what he calls “the next generation of rejuvenation therapies.” He has spent six years trying to understand what OSK really does. He says the treatment remains toxic to many cell types, and that different factors drive aging in each kind of cell. This year, he identified a gene that protects the retina from damage by free radicals, the main cause of age-related macular degeneration.

Lu’s 2020 Nature paper helped set off an investment rush, according to the magazine. Since then, US tech billionaires have placed large bets on private companies such as Altos Labs and NewLimit to explore reprogramming and anti-aging medicine. On the day of the interview, Lu had spent the morning meeting with Zhong Shanshan, one of China’s richest people, the magazine said.

Lu pushed back on the excitement around his field. He said his work with OSK was more a proof of concept than a silver bullet, and he disagreed with Sinclair’s view that humans could live to 200. “There’s just too much that goes wrong as we age,” he said. He added that the field has changed: “Six years ago, you couldn’t talk about rejuvenation. We didn’t use that word—there was pushback. But I think people have accepted the concept that you can really reverse molecular age.”