Andrew Anzalone was restless. It was late fall, 2017. The year was winding down, and so was his MD/PhD program at Columbia. Trying to figure out what was next in his life, he’d taken to long, leaf-strewn walks in the West Village. One night as he paced up Hudson Street, his stomach filled with La Colombe coffee and his mind with Crispr gene editing papers, an idea began to bubble through the caffeine brume inside his brain.
In addition to programming a piece of guide RNA to tell Crispr where to cut, you have to provide a copy of the new DNA and then hope the cell’s repair machinery installs it correctly. Which spoiler, it often doesn’t. Anzalone wondered if instead there was a way to combine those two pieces, so that one molecule told Crispr both where to make its changes and what edits to make. Inspired, he wrapped his coat tighter and hurried home to his apartment in Chelsea, sketching and Googling late into the night to see how it might be done.