# Development of miCas9 mediated gene editing therapies for cystic fibrosis

> **NIH NIH R41** · GENETOBE INC. · 2022 · $246,100

## Abstract

Project Summary
Cystic Fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane
conductance regulator (CFTR) gene. The disease affects multiple organs, with lung disease
producing most CF morbidity and mortality. Major progress has been made over the past decade
in CF drug development. Greater than 90% patients now benefit from mono or combination
therapy of several CFTR potentiators and correctors. However, these compounds neither
permanently cure the disease nor address the unmet need of the 10% null mutation carriers.
Gene editing therapy (GETx) represents a promising strategy to permanently cure the disease.
In 2019 we reported efficient gene editing on major CFTR loci in human induced pluripotent stem
(iPS) cells. In 2020, we reported the development of mi-spCas9 that has extraordinary homology
directed repair capacity. Built on these two major lines of work, here we propose to develop and
optimize a novel mi-saCas9 variant that is suitable for in vivo GETx of CF. In Aim 1, we will develop
mi-saCas9-KKH-A that is particular useful for correcting CF-causing CFTR mutations. In Aim 2
we will test two GETx strategies for CF: (i) a large size gene knock-in strategy that is suitable for
correcting all CFTR mutations; and (ii) a donor free strategy that is suitable for correcting
compound heterozygous CFTR mutations. Successful completion of the proposed Phase I work
will set a solid foundation for Phase II, in which we plan to evaluate the efficacy and safety of the
mi-saCas9-KKH-A based GETx strategies in preclinical CF animal models.

## Key facts

- **NIH application ID:** 10811304
- **Project number:** 6R41HL164205-02
- **Recipient organization:** GENETOBE INC.
- **Principal Investigator:** JIE XU
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $246,100
- **Award type:** 6
- **Project period:** 2022-08-20 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811304

## Citation

> US National Institutes of Health, RePORTER application 10811304, Development of miCas9 mediated gene editing therapies for cystic fibrosis (6R41HL164205-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10811304. Licensed CC0.

---

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