Jennifer Doudna and Fyodor Urnov have founded a company that will take on the challenge of editing rare diseases, starting with phenylketonuria.

The problem is well known: many diseases are theoretically treatable by correcting the corresponding genetic defects with the help of CRISPR tools, but doing so risks being difficult or even impossible because of regulatory rigidity and economic unsustainability. The case of the first newborn treated with a bespoke therapy developed in record time (KJ Muldoon) was a splendid proof of principle. But it left many parents of children with rare diseases asking: when will it be our turn? At the same time, specialists have long been asking: will investors return to viewing gene editing as a profitable approach worth investing in?

Fyodor Urnov wants to believe so. After promoting non-profit initiatives such as the first Center for Pediatric CRISPR Cures, he turned to the venture capital world. According to STAT News, the gene-editing pioneer reportedly said to venture capital expert Johnny Hu: “You and I both agree that, technologically, we can do this, but how do you build this into a company that actually succeeds?”. The answer came a few months later with the launch of Aurora Therapeutics. The startup begins with an initial $16 million in seed funding, the involvement of CRISPR co-inventor Jennifer Doudna, and a mission to develop gene-editing treatments also for patients with rare mutations. The goal is to launch a clinical trial in 2027, and the first test case will be phenylketonuria.

The possibility of treating this rare disease with gene editing has already been successfully explored in mice (please see The American Journal of Human Genetics and Human Genetics and Genomics Advances). The experiments, carried out using both base editing and prime editing, were led by Rebecca Ahrens-Nicklas and Kiran Musunuru, the two main architects of the treatment administered to Baby KJ for a different condition (CPS1 deficiency). The target organ is again the liver, which can be easily reached using lipid nanoparticle vectors, the same ones used for the American newborn. The gene to be repaired is PAH, which encodes the enzyme phenylalanine hydroxylase, responsible for converting phenylalanine (an essential amino acid found abundantly in dietary proteins) into tyrosine, a precursor of neurotransmitters such as dopamine. Without adequate treatment, patients with PKU must follow a very strict diet to avoid toxic accumulation of the former substance and a deficiency of the latter, with severe consequences including effects on the brain.

The mutations responsible for phenylketonuria number more than a thousand, and it would be completely unrealistic to expect the development of as many individual treatments. The only feasible approach is to develop one that can be adapted, with small modifications, to many, though not all, patients. The company’s focus will therefore initially be limited to just three mutations. The plan is to launch an umbrella trial, taking advantage of the regulatory flexibility announced in November 2025 by the Food and Drug Administration.

The field of personalized therapies is vibrant but riddled with pitfalls, and in an effort to pave the way toward a future in which the KJ case is not the exception but the rule, the United States is moving toward a regulatory paradigm shift. The idea outlined by agency leadership is to rationalize and simplify the rules for clinical trials and, ideally, for the marketing authorization of products based on “recipes” in which only one ingredient changes (the guide RNA, specific to each individual mutation), while everything else (the editor, vectors, protocols) has already been tested in relation to similar treatments. In the case of the PKU project, the genetic instructions loaded into the vector amount to about 5,000 letters, and only around twenty need to be changed to direct the correction toward a specific mutation.

The hope is that the prospect of umbrella authorizations can help restart the sector after years of pipeline contraction, the abandonment of effective but potentially low-revenue treatment candidates, and workforce reductions at companies specializing in gene editing.

A positive signal has come from the government agency known as ARPA-H, which has launched an initiative called THRIVE aimed at funding companies and research groups interested in developing precision medicine treatments for rare diseases. The landscape is indeed shifting at the academic level as well. Researchers at the Broad Institute in Boston are launching what they call a Center for Genetic Surgery. Meanwhile, at the University of Pennsylvania, Ahrens-Nicklas and Musunuru plan to start an umbrella clinical trial in 2026 targeting rare mutations responsible for urea cycle disorders, the same category of diseases that includes Baby KJ’s case. This project boasts a more personalized philosophy than that of Urnov’s company and is therefore more challenging from a commercial point of view.

(Translated and adapted from Osservatorio Terapie Avanzate)