# Human Cell Assay Core

> **NIH NIH U19** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $1,010,521

## Abstract

PROJECT SUMMARY/ABSTRACT – HUMAN CELL ASSAYS CORE
The overarching goal of this Core is to support the preclinical and IND-enabling studies in human cells with the
therapeutic leads generated in Projects 1-3. Human pluripotent stem cells (hPSCs) are a unique cell source to
generate retinal cells, tissue, and organoids. The unique attributes of hPSC model systems are particularly
critical for diseases that have high genotypic diversity, like channelopathies, as generating an animal model with
a knocked-in human allele for every patient mutation would be time and cost prohibitive and – even if
accomplished – would not provide a platform to assess potential off-target effects. Assays using hPSC-derived
cells, organoids, and tissues containing pathogenic mutations can provide patient-relevant information regarding
(1) the efficiency of intended on-target editing of mutant alleles, (2) the frequency of unintended on-target
genomic editing outcomes (e.g., large deletions, translocations) and off-target genomic editing (in both the target
cell type and other cell types exposed to the therapeutic product), and (3) the strength of functional rescue and
adverse responses. Because our proposed subretinal route of nonviral editor administration will likely deliver
payload to photoreceptors (PRs) as a cellular off-target, we developed an imaging and single cell transcriptional
pipeline to identify biomarkers of adverse events in PR-containing hPSC-derived retinal organoids (ROs),
pioneered by our team. We will apply these tools to profile potential adverse events in PRs, including changes
in phototransduction, p53 response, and innate immune response. We plan to produce iPSC-RPE suitable for
on- and off-target analysis of therapeutic editors, perform electrophysiology assays for functional
analysis of iPSC-RPE treated with therapeutic candidates, and produce hPSC-ROs for profiling potential
adverse events in human photoreceptors exposed to therapeutic candidates. The expected outcomes of
HCA Core activities include continuous provision or execution of disease-relevant, rigorous, and reproducible
human cell products and ion channel assays. We expect to leverage a world-class stem cell biology and
bioengineering community at the University of Wisconsin-Madison to pave the way to use hPSCs in IND-enabling
studies in the genome editing field. If successful, this effort could reduce the need for preclinical animal models
and provide relevant safety and efficacy information to accelerate the translation of genome editing into first-in-
human trials.

## Key facts

- **NIH application ID:** 10842298
- **Project number:** 5U19NS132296-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** David M Gamm
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,010,521
- **Award type:** 5
- **Project period:** 2023-05-16 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842298

## Citation

> US National Institutes of Health, RePORTER application 10842298, Human Cell Assay Core (5U19NS132296-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10842298. Licensed CC0.

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