# Bioengineered red blood cells as extracellular vesicle-mediated delivery platforms for gene editing machinery

> **NIH NIH UG3** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $843,298

## Abstract

Abstract
Our novel in vivo murine data uncovered a constitutive, extracellular vesicle-based feedback loop between
circulating RBCs and bone marrow precursors. Based on our results, the overall hypothesis of this application
is that bioengineered, host RBCs, loaded with custom genome editing machinery may represent an effective
approach to target and correct various molecular defects responsible for severe hemoglobinopathies and
thrombocytopathies. Our results also show that cells in either acute hypoxic environments such as ischemic
tissues, or chronic hypoxic settings such as cancers, also become targets for the RBC-EVs, expanding the
usefulness of our proposed delivery platform. Circulating RBCs are distinct among all body cells, having a
cytoplasm devoid of organelles, endo/exocytic pathways, DNA, or protein synthesis. Hence, we believe that
the RBC cytosol is an ideal carrier for the gene editing machinery components as: i) the cargo is shielded from
the immune surveillance of the host, ii) the intended target(s) of the cargo are likely not be present in
circulating RBCs, therefore unlikely to impact the cell functions, and (iii) RBCs generate extracellular vesicles
that upon fusion with target membranes transfer the EV content into the cytosol, avoiding the lysosomal
compartment. Our long term aim is to perfect our ex vivo liposome-based cell loading technology to enable us
to load a patient’s own RBCs with the “condition-tailored” combination of gene editing machinery, and
transfuse them back into the donor to target and correct the genetic condition. During the course of this project
we will: i) develop a high throughput RBC-loading method that will deliver biologicals into RBCs with minimal
effect on RBC mechanical and antigenic properties, and ii) test, in vitro the effectiveness of the bioengineered
RBCs to deliver via RBC-derived EVs a functional gene editing machinery target cells, and then validate in vivo
the efficacy of GEM delivery using a murine model first, and then a large animal model (pig).

## Key facts

- **NIH application ID:** 9984520
- **Project number:** 5UG3HL147353-03
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** IONITA Calin GHIRAN
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $843,298
- **Award type:** 5
- **Project period:** 2018-09-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984520

## Citation

> US National Institutes of Health, RePORTER application 9984520, Bioengineered red blood cells as extracellular vesicle-mediated delivery platforms for gene editing machinery (5UG3HL147353-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984520. Licensed CC0.

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