Mutations in the LMNA gene can lead to conditions such as dilated cardiomyopathy and muscular dystrophies. Most of these disorders stem from a single‑nucleotide change. Current therapies are supportive; no cure exists. New work by scientists offers a potential solution by precisely correcting the defective DNA.
Researchers led by Eric Olson at the University of Texas Southwestern Medical Center employed base editing—a tool that alters one base without cutting the DNA strand. This “pencil‑and‑eraser” technique has previously addressed other cardiac genes, but not the LMNA variants in question.
In a study reported in Proceedings of the National Academy of Sciences, the team first used base editors on patient‑derived human heart cells carrying LMNA mutations.
The group applied two distinct editors. An Adenine Base Editor (ABE) targeted the R249Q mutation responsible for cardiomyopathy, converting the wrong base back to the healthy sequence. A Cytosine Base Editor (CBE) corrected the L35P change that causes muscular disease. Both edits restored normal gene function in the cultured cells.
To test the approach in vivo, the scientists generated mice harboring the same LMNA mutations and delivered the editors via an adeno‑associated virus that homes to heart and muscle tissue. In mice with R249Q‑induced heart disease, therapy improved cardiac performance and increased survival by roughly 80 %. Mice bearing the L35P mutation were protected from developing heart disease altogether.
The authors state that this work is a key advance toward clinical gene‑editing treatments for cardiomyopathies.
Despite the promise, challenges remain, such as ensuring long‑term safety, avoiding unintended edits, and preventing immune responses. If those hurdles are overcome, a single injection could effectively cure the disease and improve patients’ lives.
Written for you by Paul Arnold, edited by Gaby Clark, and fact‑checked and reviewed by Robert Egan—this article is the result of thorough human work. We rely on readers to keep independent science journalism alive.
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