# SCGE Disease Models Studies Supplement: Development of LNP-mediated based editing to treat Leber Congenital Amaurosis (LCA) for vision restoration in mouse model

> **NIH NIH UH3** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2022 · $505,567

## Abstract

Abstract
Genetic blindness is prevalent with limited treatment options. Despite tremendous progress in the
development of editing technology as potential therapy for blindness, the ability to deliver the editing
complex into the retina for efficient editing remains a major challenge. The current prevailing method of
delivery of editing machinery is by viral vectors especially AAV. For AAV vectors, issues such as
immunogenicity, genome integration and long-term effect remain a safety concern. Further, more
complexed editing strategies including base editing (BE) and prime editing (PE), require the packaging of
multiple components into different AAVs, which further limits their efficiency. This proposal is to use
lipid nanoparticles (LNP) we have developed in the parental SCGE program for the mRNA delivery of a
base editor (ABE) to repair the mutation in a Leber Congenital Amaurosis (LCA) mouse model rd12 that
harbors a human mutation for the recovery of vision. We have previously demonstrated that the LNP
mediates the delivery of Cas9 mRNA-gRNA that targets the retinal pigment epithelium for efficient
editing. We have further demonstrated the feasibility of the LNP delivery of base editing complex by
mRNA in a mouse model. Combined, we will evaluate the application of new LNP for mRNA delivery of
the base editor and mutation correction by local subretinal injection, and correlate with the functional
restoration of vision in the rd12 mice. The success of the project will enable LNP-based transient delivery
of editing machinery to treat genetic blindness due to RPE mutations efficiently and safely.

## Key facts

- **NIH application ID:** 10620471
- **Project number:** 3UH3TR002636-05S1
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Zheng-Yi Chen
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $505,567
- **Award type:** 3
- **Project period:** 2018-09-18 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620471

## Citation

> US National Institutes of Health, RePORTER application 10620471, SCGE Disease Models Studies Supplement: Development of LNP-mediated based editing to treat Leber Congenital Amaurosis (LCA) for vision restoration in mouse model (3UH3TR002636-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10620471. Licensed CC0.

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