# Nanodelivery of functional proteins to phagosomal membranes

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2021 · $703,958

## Abstract

Project Summary
Extracellular vesicles (EVs) are cell-derived membranous structures carrying transmembrane proteins
and luminal cargo including soluble cytoplasmic proteins and nucleic acids. They are a
heterogeneous group of particles generally classified according to subcellular origin, dimension, and
tetraspanin surface expression. Circulating EVs may act as nanocontainers capable of recognizing
target cells through membrane receptors and communicating cargo through membrane fusion, a
notoriously low probability process. Interaction with recipient cells can lead to their acquisition of
EV surface proteins and luminal contents although the mechanisms controlling this exchange remain
unclear. Their complex cargo and well as surface markers are highly variable with respect to
functional impact and dependent upon the tissue context from which they are released. A central
focus of the proposed work is the isolation and identification of functionally competent small
EVs (30-150 nm) carrying an ion channel of interest which can then be transferred to a naïve,
non-expressing cell. Functionally significant EV-mediated channel translocation from one cell to
another would require a high density of channel expression per vesicle during EV biosynthesis in the
donor cell and reliable fusion with the plasma membrane and endocytic/phagocytic compartments of
recipient cells. In order to facilitate EV membrane fusion we will co-express the viral protein fusogen
hemagglutinin subtype 7 (HA). Expression of a genetically engineered blue light-activated Ca2+
channel switch (BACCS) which opens the Ca2+ selective ORAI ion channel in response to light will be
used in the design of screening strategies exploring vesicle fusion and channel transfer. The light-
sensitive probe will be used as screening tool for functional Ca2+ channel transfer in non-responsive
recipient cells via isolated EVs derived from BACCS-ORAI expressing cells. Once we have
established optimal conditions for EV-mediated channel transfer, we will leverage our experience in
the study of the anion channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR) in
murine alveolar macrophages (AMs) and epithelial cells and study the EV-mediated transfer of CFTR
to cftr-/- cells in the context of the disease of cystic fibrosis (CF) using adoptive transfer techniques.

## Key facts

- **NIH application ID:** 10115786
- **Project number:** 5R01HL125076-07
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** DEBORAH J. NELSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $703,958
- **Award type:** 5
- **Project period:** 2015-03-09 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115786

## Citation

> US National Institutes of Health, RePORTER application 10115786, Nanodelivery of functional proteins to phagosomal membranes (5R01HL125076-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115786. Licensed CC0.

---

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