# Engineering iPSC-RBCs for Transfusion

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $715,433

## Abstract

ABSTRACT: Blood transfusion is the most common therapeutic procedure performed for hospitalized patients.
Despite the efficacy of transfusion using standard donor-derived RBCs, we believe the full therapeutic potential
of blood transfusion remains untapped. Recent work from several groups has demonstrated that human
induced pluripotent stem cells (iPSCs) can be derived from small volumes of peripheral blood, can undergo
genome editing to produce precise genetic changes, and can be differentiated into terminally mature RBCs
(iPSC-RBCs), all under cGMP-compliant conditions. While iPSC-RBCs may not replace donor-derived RBCs for
routine transfusions in the foreseeable future, we believe that iPSC-RBCs that have been genetically
engineered to express novel functionalities (eg, prevention of alloimmunization in sickle cell disease patients)
could find near term clinical applications in areas where current transfusion therapies are inadequate. In the
proper therapeutic niche, engineered iPSC-RBCs would be high-value high-impact products that could sustain
high costs due to their unique characteristics. The investigative team proposes to leverage recent advances in
iPSC and genomic editing technologies, as well their ongoing NHLBI-funded studies in RBC biology and
immunology, to pursue 3 Specific Aims:
(1) To optimize cGMP-grade protocols for establishment, propagation, and differentiation of human peripheral
blood-derived iPSCs into mature RBCs (iPSC-RBCs);
(2A) To engineer iPSCs such that resulting RBCs are negative for multiple blood group antigens, and (2B) To
characterize the in vivo survival, morphological maturation, and immunogenicity of iPSC-RBCs when transfused
into specialized murine transfusion models; and
(3) To obtain FDA IND and institutional IRB approvals, and perform human autologous transfusions of iPSC-
RBCs to investigate RBC survival, maturation, and immunogenicity in recipients.
The proposed studies have been carefully designed to integrate recently developed techniques (cGMP iPSC
methods, gene editing) with specialized capabilities at Emory (EPIC cGMP clean room in the blood bank, in vivo
biotinylated RBC tracking, first-in-human cell therapy expertise) to investigate the biology of human iPSC-
derived RBCs after transfusion into human recipients. Successful completion of the proposed investigations will
lead to novel blood products to meet important unmet clinical needs in transfusion-dependent patients such as
those with sickle cell disease.

## Key facts

- **NIH application ID:** 9988483
- **Project number:** 5R01HL138656-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** John D Roback
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $715,433
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988483

## Citation

> US National Institutes of Health, RePORTER application 9988483, Engineering iPSC-RBCs for Transfusion (5R01HL138656-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9988483. Licensed CC0.

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