# Targeted Gene Delivery Systems Treating Lung Diseases

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $797,003

## Abstract

Project Summary
 This R01 proposal outlines a research plan which uses targeted nanomedicine to enhance disease-
modifying molecular mechanisms both in the acute injurious phase and in the subsequent chronic fibrotic
phase of viral-induced pneumonitis. The overall goal of this proposal is to use nanomedicine to modify specific
cellular subtypes during the lung disease process. Acute and chronic lung diseases are major causes of
mortality and morbidity in the US. Acute respiratory distress syndrome (ARDS), caused by widespread
endothelial barrier disruption and uncontrolled cytokine storm, is the major cause of death in critically ill
influenza and COVID-19 patients. Furthermore, pulmonary fibrosis, progressive scarring in injured lung, is a
major sequelae of viral pneumonia. Early analyses showed that discharged COVID-19 patients are at high risk
for developing pulmonary fibrosis. Currently, there are few pharmacological treatments that directly targets
ARDS, and available therapeutic options for pulmonary fibrosis remain suboptimal, underscoring unmet
medical needs in a heightened state due to COVID-19 pandemic. Strongly supported by our published and
unpublished in vivo results, we believe that targeted nanomedicine approaches have tremendous potential to
treat ARDS and pulmonary fibrosis, which will be comprehensively tested in vivo in this application. Aim 1 will
test the therapeutic effectiveness of specifically reducing endothelial dysfunction in acute lung injury (influenza
or SARS-CoV-2) in mice and perfused human lungs using a VCAM1-targeting, KLF2 mRNA-encapsulated
nanoparticles. We anticipate that specific endothelial KLF2 overexpression will reduce acute lung injury. Aim 2
will test the therapeutic effectiveness of specifically targeting lung fibroblasts in chronic pulmonary fibrosis
(bleomycin) in mice and human lung slices using PDGFRB-targeting nanoparticles to deliver shRNAs against
TXNDC5. We anticipate that specific fibroblast inhibition of TXNDC5 will reduce lung fibrosis.

## Key facts

- **NIH application ID:** 10522016
- **Project number:** 1R01HL159558-01A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** MATTHEW TIRRELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $797,003
- **Award type:** 1
- **Project period:** 2022-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522016

## Citation

> US National Institutes of Health, RePORTER application 10522016, Targeted Gene Delivery Systems Treating Lung Diseases (1R01HL159558-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10522016. Licensed CC0.

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