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A close partnership between academic institutions, industry, and the FDA helped develop within a record-breaking six months a personalized treatment designed to save the life of a baby. That’s a key message behind a talk by Max Sellman, senior product manager for gene editing at Aldevron, who provided a behind-the-scenes look at the manufacturing process on Wednesday at the BioProcess International (BPI) Conference in Boston.The story of KJ Muldoon, a baby given the world’s first personalized mRNA-based CRISPR therapy, hit the news in May. Born with a rare single-gene mutation affecting his metabolism, he had a grim prognosis before the collaboration formed.

“We didn’t do this as a money maker,” explains Sellman. “We did it because we could help this patient and, as a field, we needed to demonstrate the promise of CRISPR drugs.”
The collaborators were especially keen to show how CRISPR drug development is modular, meaning their platform can be rapidly repurposed to treat multiple single-gene disorders. “If you can sequence it, you can cure it, but the drug is only as good as how quickly you can develop it,” he continues.With urea cycle disorders (UCD), such as KJ’s lack of the CPS1 enzyme needed to remove ammonia from the body, even a single day is critical to preventing irrevocable neurological damage and death. “If it takes years from sequencing the patient to when you treat them, have you really helped?” he asks.

Accelerated timeline

According to Sellman, the standard timeline for developing gene-editing products is a couple of years, whereas from the time the team at Children’s Hospital of Philadelphia (CHOP) first encountered KJ to dosing him took only about six months.Critical to developing the N of 1 therapy were products and services Aldevron and sister company Integrated DNA Technologies (IDT) have developed for the production of mRNA therapies over years, points out Sellman.These allowed Aldevron to manufacture an mRNA-encoded base editor, IDT to design a custom guide RNA and off-target safety services, and partner company Acuitas to supply a clinically validated lipid nanoparticle (LNP) formulation.“The collaboration was also a totally new model,” Sellman says. “Instead of being a service provider, we were working with a seat at the table, trying to do everything efficiently outside of typical timescales.”The collaboration also worked closely with the FDA to streamline regulatory development for their single patient.

“With patients in this ultra-rare disease space, well-motivated academics sometimes start a clinical trial with no intention of commercialization  but still adhere to FDA guidelines written with larger trials [and reproducibility] in mind,” he states, adding that under a compassionate use framework, the drug was fast tracked for approval. “Our teams demonstrated an approach that was safe and high quality, but with commonsense trade-offs to go faster in this life-and-death situation,” he says.
Aldevron now hope to work with the industry to codify their approach. “If your passion is for knocking down rare genetic diseases and using gene editing to accomplish it, we’re building a platform for that,” says Sellman.
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