# SCGE Disease Models Studies Supplement: Correction of RHO P23H adRP

> **NIH NIH U42** · UNIVERSITY OF MISSOURI-COLUMBIA · 2022 · $494,470

## Abstract

Project Summary
The broad, long-term objective of this work is to establish a rubric to evaluate safety and
efficacy of somatic cell genome editing technologies. These goals will be addressed in
the context of an experimental therapy for retinitis pigmentosa caused by the RHO
P23H variant. The specific aims of this proposal address refinement of the therapeutic
window for this therapy, the minimum number of cells that must be edited to save vision,
and the general safety of the therapeutic strategy. These aims will be met through the
use of AAV5 to deliver an engineered meganuclease that specifically targets the
dominant P23H allele while saving the wildtype allele that differs by only one base. This
reagent will be evaluated in a validated, rapidly progressing swine model that harbors a
human RHO P23H transgene. A previously optimized dose that produces a durable
response will be delivered via subretinal injection and the animals will be followed for 32
weeks to repeatedly measure effectiveness over time via clinical eye exam, Full-Field
Electroretinogram (ffERG), and Optical Coherence Tomography (OCT). At the end of
the experiment, eyes will be examined via immunohistochemistry (IHC) to determine the
regional, minimum number of rods that must be edited to save cone function and
therefore to save vision. These experiments will be performed at two different stages in
disease progression that are hypothesized to represent the last treatable state and the
first non-treatable state so that guidance can be provided for criteria of enrollment of
patients in a future clinical trial. In parallel, animals will be similarly treated and then
sacrificed at two weeks post injection to determine the range of adjacent tissues to
which the AAV5 vector will migrate. These animals will also be used to determine the
level of editing that occurs in non-intended tissues, including the germline. All animals
will be used to obtain data on general physiological response to the therapy.

## Key facts

- **NIH application ID:** 10619167
- **Project number:** 3U42OD027090-04S2
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** RANDALL S PRATHER
- **Activity code:** U42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $494,470
- **Award type:** 3
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10619167

## Citation

> US National Institutes of Health, RePORTER application 10619167, SCGE Disease Models Studies Supplement: Correction of RHO P23H adRP (3U42OD027090-04S2). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10619167. Licensed CC0.

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