# Plug-and-Play HLA for Safer and Personalized Off-the-Shelf Cell Therapies using big-DNA technology

> **NIH NIH R43** · NEOCHROMOSOME, INC. · 2021 · $300,000

## Abstract

Neochromosome Inc, Confidential
PROJECT SUMMARY
Cellular therapies hold great promise for combating previously intractable diseases (e.g., cancer, organ failure,
neuropathy, etc.). While autologous (patient-derived) cells generally are optimal, this route remains limited for
many applications, cost-prohibitive, and burdensome. Allogeneic (donor-derived) pluripotent stem cells (PSCs),
which can be differentiated to any cell type, provide greater scalability and cost savings. However, allogeneic
cells are limited by the need to match HLA Class-1 alleles, the most genetically polymorphic region in humans.
Mismatches in HLA Class 1 haplotypes lead to the "self vs non-self" immune response that can result in
rejection of transplanted therapeutic cells. In this Phase I SBIR proposal, we will address this unmet need by
developing a technology to program any HLA haplotype into a PSC on-demand. Our "immune-matching"
technology will provide isogenic PSCs compatible with any individual, especially those with rare HLA
haplotypes under-served by PSC "banks". Such engineered cells can be centrally manufactured into any
differentiated cell type (eg, neurons, muscle, etc). Before differentiation, the PSC can also be modified with
additional genetic safeguards and efficacy enhancing features beyond just HLA Class 1 genes, thus reducing
time and effort. We will establish proof-of-concept of this technology during this Phase 1 SBIR with the
following goals: (1) Using gene editing, we will generate a blank human PSC line devoid of HLA-1 proteins,
capable of accepting a new HLA-1 haplotype; (2) We will reconfigure and synthesize HLA Class 1 as a single
linked 115-kb locus, with modular assembly features for inputting any patient haplotype on-demand; (3) We will
demonstrate integration of our 115-kb donor HLA Class 1 locus into our blank stem cell line, while preserving
the native regulatory information and expression levels of the HLA Class 1 genes. Once developed, our
technology will provide personalized stem cells for both immunotherapy and regenerative medicine
applications, leading to more efficacious and safer cell-based treatments. We anticipate licensing our
technology to other companies as a cost-effective resource for allogeneic cell therapies.

## Key facts

- **NIH application ID:** 10137888
- **Project number:** 5R43AI148008-02
- **Recipient organization:** NEOCHROMOSOME, INC.
- **Principal Investigator:** Leslie Mitchell
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,000
- **Award type:** 5
- **Project period:** 2020-05-02 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137888

## Citation

> US National Institutes of Health, RePORTER application 10137888, Plug-and-Play HLA for Safer and Personalized Off-the-Shelf Cell Therapies using big-DNA technology (5R43AI148008-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10137888. Licensed CC0.

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