Crispr Pioneer launches startup to make personalized gene-editing therapies

Last February, A The sick infant named KJ received a gene-editing treatment created specifically for him. Created in just six months, it was intended to correct a rare genetic mutation that was causing toxic ammonia to build up in his tiny body. The treatment likely saved his life, and baby KJ was released from the hospital in June.

Now, a new startup called Aurora Therapeutics, co-founded by gene editing pioneer Jennifer Doudna, aims to expand these treatments to include a greater number of patients with rare diseases. Doudna is one of the inventors of the gene editing system known as CRISPR, and she won the Nobel Prize in 2020 for her work on this technology.

Aurora plans to take advantage of the new regulatory pathway announced by FDA officials Marty McCurry and Vinay Prasad in the fall. The new program, called the “Plausible Mechanism Pathway,” allows the FDA to approve personalized treatments for rare and fatal diseases based on data from a small number of patients, McCurry and Prasad reported in an article in the New England Journal of Medicine.

Typically, new drugs must be tested on hundreds, if not thousands, of patients in order to gain regulatory approval. For drug trials for rare diseases, it is difficult to recruit such a large number of patients because so few people have the disease. The new FDA pathway provides a way to approve these types of drugs when a large randomized trial is not possible.

“Once a manufacturer demonstrates success with several consecutive patients with different personalized treatments, the FDA will move toward granting marketing authorization for the product,” Makari and Prasad say in their article. Pharmaceutical companies will then be able to use data from these patients to get similar drugs approved based on the same basic technology.

This is key for Aurora, which will initially focus on treating a metabolic disorder called phenylketonuria, or PKU, which is screened for at birth. The disease leads to toxic levels of phenylalanine, one of the basic components of protein, in the blood. Patients with phenylketonuria (PKU) must follow a highly restrictive low-protein diet. Without early treatment and monitoring, phenylketonuria can stunt brain development and impair cognitive function. It is estimated that 13,500 people in the United States are living with this disease.

“There are a lot of patients who could benefit from this treatment,” says Edward Kay, CEO of Aurora Therapeutics and a pediatric neurologist. “But the problem is that you have many, many mutations — more than a thousand — that cause this disease.”

Crispr works by using guide RNA to deliver an editing molecule to the desired location in the genome. Guide RNA is like a GPS in a car: it goes where it is programmed to go. In baby KJ’s case, scientists built an RNA guide to target his specific genetic mutation. That’s why his treatment only works for him.

Aurora’s strategy involves replacing this guide RNA to produce several versions of the PKU treatment that address different mutations. Previously, the FDA considered each version an entirely new drug, and each required its own clinical trial. But now, Aurora will be able to use the same technology platform to treat many of the mutations that cause phenylketonuria (PKU) with fewer regulatory procedures.

Kay says the company will use base editing, a more precise form of CRISPR, and will have a standardized process to simplify the design and manufacturing of its treatments.

“We care deeply about not leaving any mutation behind,” says Fyodor Urnov, co-founder of Aurora and a genome editing scientist at UC Berkeley. Urnov and several colleagues at Berkeley’s Innovative Genomics Institute, which Doudna established in 2015, co-designed KJ’s treatment.