Molecular therapy. AdvancesJul 23, 2026

Restoring eye cell function in choroideremia by delivering mRNA to the retina

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 24, 2026

Abstract

Subretinal delivery of human CHM-mRNA using lipid nanoparticles achieved detectable expression for up to 15 days post-injection.

Non-viral mRNA delivery may offer a safer and more cost-effective strategy for gene therapy in inherited retinal diseases.
The approach effectively targets retinal pigment epithelium and choroid, with a lower inflammatory response compared to traditional viral vectors.
Restoration of REP1 levels and correction of Rab prenylation defects were observed in human stem cell-derived retinal cells and a mouse model of choroideremia.
Functional rescue of retinal activity was demonstrated through electroretinography 24 hours after injection of hCHM-mRNA.

Simplified

Inherited retinal diseases (IRDs) represent a major cause of blindness, yet current viral vector-based gene therapies are limited by high cost, restricted cargo capacity, and safety concerns related to immunogenicity. We explore here retinal delivery of non-viral, in-vitro-transcribed mRNA using lipid nanoparticles (LNPs) as a safe, cost-effective gene augmentation strategy for choroideremia (CHM). CHM is an X-linked IRD caused by loss-of-function mutations in CHM that encodes Rab escort protein-1 (REP1), which is essential for Rab GTPases prenylation and intracellular trafficking. We demonstrate that subretinal delivery of human CHM-mRNA (hCHM-mRNA) efficiently targets the retinal pigment epithelium (RPE) and choroid, achieving expression that is detectable up to 15 days post-injection, with lower and transient inflammatory response compared to AAV2 vectors. Furthermore, hCHM-mRNA delivery in vitro to human induced pluripotent stem cell (hiPSC)-derived RPE cells from a CHM patient and in vivo via subretinal injection in the Chm ^± mouse model successfully restored REP1 levels and reversed Rab prenylation defect. Concordantly, Chm ^± treated with hCHM-mRNA showed functional rescue of retinal activity measured by electroretinography 24 h post-injection. Overall, these results provide a strong proof-of-concept for LNP-mediated mRNA technology in the retina, supporting the development of scalable, non-viral gene approaches for IRDs, including CHM.