# Improving Xenogeneic Chimerism and Tolerance through Genome Engineering Technology

> **NIH NIH P01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $302,398

## Abstract

Summary
Shortage of available allogeneic donor organs represents the greatest unmet medical need in the field of
transplantation today. The survival of pig-to-primate organ transplants has improved markedly over the past
three decades but unfortunately remains insufficient for clinical application. Further progress in this field will
likely depend upon genetic modifications of porcine source animals both to overcome molecular
incompatibilities with primate recipients and to allow the induction of immunological tolerance. The objectives
of this proposal are to produce such pigs and to identify additional genetic modifications that will help attain the
goal of clinically relevant xenograft survival. Advanced genetic engineering techniques, including site-specific
recombinase-driven gene additions and edits using the precision CRISPR-Cas9 system, will be used to
effectively deliver multiple genetic modifications affecting complement activation, coagulation and barriers to
induction of mixed hematopoietic chimerism to achieve tolerance. These modifications will be made efficiently
and rapidly by applying state-of-the-art genomic sequencing and guide RNA design specifically tailored to the
highly inbred MGH miniature swine to be engineered. Genetically modified pigs incorporating the new
modifications will be tested in Projects 1, 2, and 3 for efficacy in promoting organ survival and mixed chimerism
for tolerance induction in primate and humanized mouse models.

## Key facts

- **NIH application ID:** 9987467
- **Project number:** 5P01AI045897-20
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Stevens Sean
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $302,398
- **Award type:** 5
- **Project period:** 2000-09-15 → 2022-01-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987467

## Citation

> US National Institutes of Health, RePORTER application 9987467, Improving Xenogeneic Chimerism and Tolerance through Genome Engineering Technology (5P01AI045897-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9987467. Licensed CC0.

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