# Engineered Protein Oxygen Carriers: a novel blood substitute for trauma care

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2020 · $202,500

## Abstract

There is a pressing need for artificial oxygen (O2) carriers as an alternative to donated blood/blood
products. For victims of life-threatening hemorrhage, transfusion is the most effective treatment, yet
nearly 25% of the nation's blood centers are perennially in short supply. Additionally, the perishability of
blood products coupled with blood's potential for immunologic reactions, makes the transfusion of blood
products highly problematic in non-hospital settings. The issue of timely access to blood is particularly
challenging in austere environments (i.e. battle field, rural site) where lengthy transports to definitive
care may be required. Unfortunately, failure to transfuse blood within the “golden hour” increases the
risk of poor clinical outcomes including death.
 The proposed studies aim to use modern advances in de novo designed artificial heme proteins
to over come the design limitations of earlier emergency blood substitutes based on natural hemoglobin..
Engineered Protein O2 Carriers (EPOCs) are inherently more adaptable than hemoglobins, allowing
direct control of gaseous ligand affinity. EPOCs also offer control over thermal stability (autoclavability),
molecular weight and net charge (blood clearance rates), density of O2 binding sites per protein
(transport capacity) as well as other desirable physical properties. Importantly, our preliminary results in
a rodent hemorrhagic shock model suggest that EPOCs enhance tissue oxygen deliver compared to
standard lactated Ringers resuscitation.
 This proposal will use diverse amino acid substitutions at three specific sites in contact with the
O2 binding hemes in the EPOC frame to generate a large library of EPOC variants. These variants will
be rapidly screened to select three EPOCs with high, medium, and low O2 affinity, while maintaining tight
heme binding. They will also be selected for low nitric oxide binding to avoid potential counterproductive
vascular constriction. An initial screening trial in rats using EPOCs to replace blood lost to hemorrhage
will identify if any of the three classes of O2 affinities performs better than our current EPOC in circulation.
The leading EPOC candidate will then be tested in larger rat trials for pharmacological safety, blood
stability and clearance, and potential immunogenicity or toxicity. Another series of rodent trials will
quantitate EPOC efficiency at treating severe hemorrhagic shock, in both a shock model with controlled
bleeding and a freely hemorrhaging liver laceration shock model.
 By establishing the best properties for EPOCs in circulation and establishing their safety and
efficacy, we will provide the means necessary to build a safe, effective and durable O2 carrier with the
ultimate goal of expanding the nation's access to emergency “blood” products and revolutionizing
transfusion medicine.

## Key facts

- **NIH application ID:** 9899822
- **Project number:** 5R21HL144224-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Bohdana Discher
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $202,500
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899822

## Citation

> US National Institutes of Health, RePORTER application 9899822, Engineered Protein Oxygen Carriers: a novel blood substitute for trauma care (5R21HL144224-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9899822. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*