Aditya Raguram still remembers the lecture well.
It was his junior year at Harvard and the instructor, David Liu, was describing something called “directed evolution” — a way of putting Darwin’s principles of natural selection to work in a test tube to create proteins with never-before-seen functions. Liu’s lab had just used it to invent the first base editor — a version of CRISPR that cleanly switches just one DNA letter.
That was the moment Raguram, who’d taught himself to code Python as a middle school student in New Jersey and always envisioned going into math or physics, caught the biology bug.
By the next year, he was working in Liu’s lab. While still an undergraduate, he helped improve base editors so they would make fewer off-target mistakes. He stayed on for a Ph.D., contributing to the invention of prime editing before turning to one of the biggest problems preventing all these new DNA-manipulating micromachines from becoming miracle cures: delivery.
Viral vectors are good at getting into cells, but can prompt dangerous immune responses. Lipid nanoparticles are much safer, but they can only target a few tissues. Raguram took up an idea that combined the best of both worlds — virus-like particles — and engineered next-generation versions capable of efficiently transporting CRISPR proteins into different tissues including the brain.
Now a fellow at the Whitehead Institute, Raguram’s shifting focus to studying how human cells shuttle proteins around the body, with hopes of unlocking new, safer ways of getting all flavors of CRISPR into cells. “I’m really excited to see what new insights we might be able to learn from these endogenous systems,” he said.
— Megan Molteni
