AAV Gene Therapy Shows Promise for Treating LRAT-Associated Retinitis Pigmentosa

March 10, 2026 —

Researchers have reported a significant advance in AAV gene therapy for inherited retinal diseases, demonstrating promising results in a preclinical study targeting retinitis pigmentosa (RP) caused by mutations in the lecithin:retinol acyltransferase (LRAT) gene. The research, led by El-Kalaani and colleagues, highlights the potential of gene replacement therapy to restore retinal structure and function in a severe form of this vision-threatening disorder.

Retinitis pigmentosa is a group of inherited retinal diseases characterized by the gradual degeneration of photoreceptor cells, eventually leading to progressive vision loss and blindness. While supportive treatments can help manage symptoms, effective disease-modifying therapies remain limited. Mutations in the LRAT gene, which plays a key role in the visual cycle, are known to cause early-onset retinal degeneration and represent an important target for therapeutic intervention.

In the study, scientists used an adeno-associated virus (AAV) vector to deliver a functional copy of the human LRAT gene directly into retinal cells. AAV vectors are widely used in ocular gene therapy because of their strong safety profile, low pathogenicity, and ability to support stable gene expression in sensitive tissues such as the retina.

The therapy was tested in a Brown Norway rat model carrying a mutation in the Lrat gene that closely resembles a mutation found in certain human patient populations. Researchers delivered the AAV gene therapy through subretinal injection, targeting the retinal cells most affected by the genetic defect.

Following treatment, the animals showed significant preservation of retinal structure compared with untreated controls, suggesting that the therapeutic gene was successfully expressed and able to counteract the degenerative effects of the mutation. Functional testing also demonstrated improved electrophysiological responses to light stimuli, indicating that treated photoreceptor cells regained the ability to respond to visual signals.

Importantly, behavioral testing revealed that treated animals performed better in vision-guided tasks, suggesting that the improvements in retinal structure and function translated into meaningful visual benefits.

The findings provide strong proof-of-concept for AAV-mediated gene replacement therapy in LRAT-associated retinitis pigmentosa and highlight the broader potential of AAV vectors for treating monogenic retinal diseases. However, the researchers note that additional studies will be necessary to evaluate long-term safety, immune responses to viral vectors, and the durability of gene expression before clinical trials can begin.

Overall, the study represents a promising step forward in the development of AAV gene therapies for inherited blindness, offering hope that precision genetic medicine could eventually restore vision for patients affected by LRAT-related retinal degeneration.