# Development of Swine Reporter Models for Testing Somatic Cell Genome Editing Tools

> **NIH NIH U24** · RECOMBINETICS, INC. · 2021 · $781,473

## Abstract

PROJECT SUMMARY
 Precise gene inactivation, gene addition, and gene repair in patient cells are all part of a new paradigm
in gene therapy. However, the full potential of these gene editing therapies can only be realized when it
becomes possible to treat each tissue directly in the body of the patient. This goal requires novel gene editing
delivery vehicles and routes of administration where uptake kinetics, penetration, and distribution are well
established. A first step to achieve this goal is to develop model animals that mimic size, physiology, and
aging of human patients. Swine models meet these criteria to enable in utero, pediatric, and adult gene editing
therapies. Accordingly, Recombinetics has been using gene editing to create a suite of swine models with
humanized disease alleles for the past 6 years to augment preclinical research and development. While these
models are valued for efficacy studies, findings from these animals are not broadly applicable for optimization
in vivo editing. To address this limitation, we propose to develop a suite of swine models and vectors capable
of reporting gene-editing outcomes with a combination of in vivo (whole animal) and single cell readouts. Our
modular design and production pipeline will enable rapid and reliable modeling of most human disease alleles
within a single reporter system.
 The proposed models will report outcomes of two types of gene editing tools: 1) those that cut or nick
DNA to stimulate DNA repair, ie. CRISPR/Cas9, TALENs, ZFNs, and 2) base-editors that convert selected
DNA bases to another base at the target site without creating a double strand break. The validated reporter
constructs will be integrated into the swine genome at one of three safe-harbor loci prior to animal production
by somatic cell nuclear transfer (cloning). Reporter activity in these founder animals and their offspring will be
characterized by whole body imaging and single cell analysis. The validated reporters, associated data, and
animal models will then be provided to the Somatic Cell Gene Editing consortium for distribution. These novel
models will enable new discoveries to characterize therapeutic delivery, DNA repair preferences, and off-target
risk for any tissue or cell type in the body.
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## Key facts

- **NIH application ID:** 10246881
- **Project number:** 5U24OD026641-04
- **Recipient organization:** RECOMBINETICS, INC.
- **Principal Investigator:** Daniel Fred Carlson
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $781,473
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246881

## Citation

> US National Institutes of Health, RePORTER application 10246881, Development of Swine Reporter Models for Testing Somatic Cell Genome Editing Tools (5U24OD026641-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246881. Licensed CC0.

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