AUF1 Gene Therapy Limited Muscle Loss After Injury in Mice

Severe muscle injuries, from accidents, sport or surgery, often heal badly: the muscle shrinks, scars and loses strength. No approved drug promotes the regeneration itself. A study published in Molecular Therapy, online on February 23, 2026 and in the June 3 issue, tests a different idea in mice: give injured muscle more of a protein called AUF1, which helps control which messenger RNAs a cell keeps and which it destroys. The work comes from a laboratory at NYU Grossman School of Medicine and is the scientific basis of Regerna Therapeutics, a New York startup. Everything below happened in mice.

What AUF1 does

AUF1 is an RNA binding protein. It attaches to stretches rich in the letters A and U at the end of certain messenger RNAs and either speeds their destruction or stabilizes them. Many of those messages encode the switches of myogenesis, the process by which muscle stem cells, called satellite cells, wake up, multiply and rebuild fibers. AUF1 is barely detectable in healthy muscle fibers but rises in activated satellite cells, and earlier work from the same group showed that mice lacking it lose muscle faster with age and repair injuries poorly.

What the study measured

The team delivered extra AUF1 to mouse muscle in three ways: a muscle targeted viral vector, AAV8, injected into the bloodstream a month before injury; the same vector injected into the muscle; and messenger RNA packaged in lipid nanoparticles, the delivery system used in mRNA vaccines, injected into the muscle 24 hours after injury. The injuries were induced experimentally and were severe.

According to the abstract, all three approaches were highly effective at blocking muscle atrophy and speeding regeneration. Tissue, electron microscopy and biochemical analyses showed less atrophy, faster regeneration and restored nerve connections. Treated mice kept near normal muscle strength and function, while untreated mice showed a significant, persistent loss of strength. RNA sequencing and analysis of which messages were being translated pointed to more activity in contraction and repair genes and less in inflammation. The authors report no negative safety signals in the mice, including no sign of tumors.

What is still hypothetical

The step from mouse to human is large here for specific reasons. Mice regenerate muscle more readily than older people do. A viral vector given into the bloodstream raises questions of dose, immune response and how long the gene stays active, which are not settled by a mouse result. Lipid nanoparticles injected into muscle are better understood, but the dose needed for a human limb is unknown. And the full text of the paper sits behind a paywall; this article relies on the abstract, the introduction and the declarations that the publisher makes public.

What a human trial would still need

Before a first human trial, a company would typically need toxicology studies in at least one more species, manufacturing under drug standards, and an investigational new drug application cleared by the FDA. An earlier stage of this program is on the record: a 2025 essay in Science describes a research agreement with the gene therapy company REGENXBIO, from March 2021 to September 2023, with about $2 million in support, aimed at an investigational new drug for AUF1 in Duchenne muscular dystrophy. A related patent application, AU2022313258A1, on AUF1 combination therapies, lists New York University as assignee and is still pending.

On its LinkedIn company page, Regerna describes two programs: REG-1003, AUF1 delivered by lipid nanoparticles, for disuse atrophy after surgery or injury, and REG-A40, AUF1 delivered by AAV8, for muscular dystrophies. Those are the company's own descriptions and have not been checked against independent sources.

The authors' declaration of interests is explicit: two authors are cofounders of Regerna Therapeutics and hold equity in it, and both have filed a patent application related to this work. NYU Langone Health says it reviewed and approved those arrangements under its conflict of interest policy. For another approach to keeping muscle, tested in people, see our piece on myostatin blockers during GLP-1 treatment.

I read this as a careful mouse study with a clear mechanism and a long road ahead. The useful result is that the mRNA version worked when given a day after injury, which is the timing that would matter in real care. What it cannot tell anyone yet is whether the effect survives the jump to larger animals and then to people, and that is the only question that decides whether this becomes a treatment.

Disclosure: The author has a personal connection to the company.