Eye Cells May Have Been Rejuvenated for the First Time in People

Full reprogramming with the four Yamanaka factors comes with a risk of cells growing out of control and forming teratomas, a type of tumor that can sprout partially or fully developed tissues like teeth, muscle, and bone. Sinclair’s goal was to exploit this reprogramming process to help cells regain their proper instruction manual, and together with his graduate student Yuancheng Lu, launched studies involving just three of the genes, dropping one that is most associated with cancers. There was no guarantee that using three of the factors would trigger reprogramming, since all of the previous studies employed all four. And for three years, Lu learned why—while working with mice with age-related vision loss like glaucoma, he struggled to reprogram retinal ganglion cells with only three of the factors. Experiment after experiment failed. Frustrated, Lu sought out Sinclair, hoping to move onto another project. “He said reversing aging is probably the hardest biological question in the world, and if it were easy, it would have been done already,” Lu says. But there was at least one element working in Lu’s favor. “Removing the fourth factor allowed the three other factors to be small enough to fit into the viral tool we used to deliver them into [animals],” he says. “If the three genes were a little bigger, then we couldn’t fit them into the viral vector.”