Rewrite and Replace: Shakked Halperin, Serial Entrepreneur

By Niki Borghei.

Shakked Halperin
Shakked Halperin, founder of Rewrite Therapeutics and Replace Therapeutics.

In February 2022, Rewrite Therapeutics, founded by Shakked Halperin, PhD and known for its DNA-writing technology, was acquired by Intellia Therapeutics. But Shakked isn’t one to take it easy! Just a few weeks prior, he had already founded his second company: Replace Therapeutics, which soon found a home at Bakar Labs.

Both of Shakked’s companies use CRISPR to target specific regions in the genome, but differ from conventional methods by avoiding double-stranded breaks in DNA and fusing additional enzymes to enable precision editing.

“CRISPR offered a pair of DNA scissors that were going to change the world,” Shakked says. “But I didn’t want to just cut. I wanted to rewrite with full control over the target sequence, so with Rewrite I turned to nature’s DNA writer – DNA polymerases – and made something closer to a pencil.”

The problem? Polymerases make mistakes. Not only can writing edits directly in the cell create errors, but cells are good at blocking these edits. At Rewrite, Shakked realized it would be more precise and efficient if, instead of writing the DNA inside the cell, he could develop a way to glue a pre-synthesized sequence of DNA containing the edit in the right spot.

Shakked and his team got right to work. They launched Replace to develop this “DNA glue” using DNA ligases.

Did Shakked get whiplash from the quick turnaround from Rewrite to Replace? No. The transition was seamless — same investors, lawyers, even some of the same scientists — “We never stopped running,” he says.

Shakked moves fast, and the Bakar Labs community offered him a support system that helped make this happen.

“When you just get started, there are so many things to get set up before you can get to the science,” he says. “Bakar Labs takes care of so much of it, all with the collaborative and supportive culture of academia due to its close ties with Berkeley.”

Replace was recently acquired by Tome Biosciences, a deal announced on January 2 of this year. Shakked is now moving on to new ventures, but his story still serves as inspiration for the Bakar Labs community.

“Shakked and his team are seasoned, having had stellar success with a prior startup,” says Gino Segrè, managing director of Bakar Labs. “When they came to Bakar Labs, after having tried another incubator, it was a validation that the community and the capabilities we offer startups makes a big difference. It’s gratifying to be able to help such talent.”