# Molecular Therapies for Cystic Fibrosis Lung Disease

> **NIH NIH P01** · UNIVERSITY OF IOWA · 2022 · $2,311,617

## Abstract

OVERALL COMPONENT
PROJECT SUMMARY
Cystic fibrosis (CF) is a common life-shortening genetic disease that causes progressive lung failure due
to recurrent infections and airway obstruction. While our knowledge of CFTR function has advanced
greatly in the 30 years since the discovery of the gene, treatments for the disease remain suboptimal and
CF remains progressive and fatal. Advances with small molecule CFTR modulator therapies have
helped restore protein function for many mutations, but approximately 10% of people with CF have not
benefited from these strategies, including people with nonsense and splicing mutations. The central
theme of this proposal is developing new molecular therapies to prevent or treat CF lung disease.
The goal of our three projects and four cores is to exploit the power of our in vitro and animal models to
address questions fundamental to lung disease pathogenesis and to use this knowledge to inform new
therapeutic strategies to complement CF defects, including gene repair and the addition of a small
molecule that forms anion channels. The three closely interrelated Projects will work together to
accomplish the following goals: 1) To restore CFTR function using targeted single nucleotide
editing. We hypothesize that cells in the surface airway epithelium, including those with progenitor
capacity, can be targeted to repair CFTR mutations using base editing. 2) To understand the
mechanisms of amphotericin B (AmB)-induced anion secretion in airway epithelia and to test the
hypothesis that AmB can restore CF host defenses in vivo. AmB is a small molecule that forms
anion channels. 3) To determine how CFTR expression in pulmonary ionocytes and ciliated cells
regulates properties of the airway surface liquid that are crucial for clearance and innate
immunity. The development of effective gene therapies for cystic fibrosis lung disease must be guided
by a clear understanding of pathophysiologic mechanisms of disease and the relevant cellular targets for
CFTR gene replacement or editing.
The Project Leaders and their teams have outstanding track records of collaborative CF research, and
here they sharpen their focus to a common goal. Their highly creative research is supported by four
cores that provide innovative infrastructure and services. Through these studies we hope to accelerate
the development of new therapeutics for CF lung disease.
!

## Key facts

- **NIH application ID:** 10470331
- **Project number:** 5P01HL152960-03
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** PAUL B MCCRAY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,311,617
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470331

## Citation

> US National Institutes of Health, RePORTER application 10470331, Molecular Therapies for Cystic Fibrosis Lung Disease (5P01HL152960-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10470331. Licensed CC0.

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