# Large Animal Core

> **NIH NIH U19** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $272,729

## Abstract

PROJECT SUMMARY/ABSTRACT – LARGE ANIMAL CORE
To achieve the aims of the CRISPR Vision Program, it will be critically important to determine acceptable dosage
and toxicity levels (if any) of therapeutic candidates using nonhuman primates (NHPs). The NHP eye has much
greater similarity to the human eye than that of any other species commonly used for research and drug testing.
For example, the NHP is the only non-human mammal that has a macula. In humans, the macula is susceptible
to a number of pathological conditions such as age-related macular degeneration and is often the part of the
human retina most adversely affected by drug toxicity. Hence, evaluating the effects of test articles containing
genome editors on the NHP eye, and the macula in particular, will be highly informative for safety assessments
by the FDA. The Large Animal Core will provide the surgical and in vivo testing expertise to determine the
suitability and practicality of the proposed subretinal dosing route in NHPs. The Large Animal Core will also
monitor the NHPs during and after test article dosing for signs of both local (i.e., proximal to the subretinal bleb)
and distal retinal and general ocular toxicity. The animals will be monitored for behavior and other indications of
systemic toxicity, as well. The Core will be administered under the following three Tasks to support all of the
CRISPR Vision Projects. In Task 1, the Large Animal Core will administer the test article subretinally in a
surgically sterile manner using a trans-vitreous approach, small-gauge pars plana vitrectomy equipment, and
automated subretinal injector. In Task 2, the Large Animal Core will perform in vivo toxicity evaluations. The
animals will be monitored both functionally and morphologically for in vivo signs of ocular toxicity following
subretinal dosing. Photopic and scotopic full-field electroretinography (ERG) testing will determine the health of
the entire retina. Photopic multifocal ERG will be used to assess possible localized retinal injury, either from the
subretinal injection procedure itself or localized toxicity of the test article. Morphological determinations will
include ocular examinations, color fundus photographs, fluorescein angiography and spectral domain optical
coherence tomography. In Task 3, the Large Animal Core will perform necropsy and eye retrieval for purposes
of determining drug distribution and histopathological signs of drug toxicity. The expertise and centralization of
these studies in the Large Animal Core will ensure efficient, standardized assessment of lead therapeutic
products nominated by all three CRISPR Vision Program Projects, with near real-time data return to inform
Project evolution. The extensive history of the Core Lead, Dr. Nork, with developing methods for subretinal
injection and ocular evaluations will provide nimble protocol innovation if required over the span of the partner
Projects.

## Key facts

- **NIH application ID:** 10842301
- **Project number:** 5U19NS132296-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** T MICHAEL NORK
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $272,729
- **Award type:** 5
- **Project period:** 2023-05-16 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842301

## Citation

> US National Institutes of Health, RePORTER application 10842301, Large Animal Core (5U19NS132296-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10842301. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*