Durable Reconstitution of Sinonasal Epithelium by Transplant of CFTR Gene Corrected Airway Stem Cells

Overview

Journal bioRxiv

Date 2025 Feb 3

PMID 39896581

Authors

Dawn T Bravo

Sriram Vaidyanathan

Jeannette Baker

Vrishti Sinha

Esmond Tsai

Pooya Roozdar

William W Kong

Patrick J Atkinson

Zara M Patel

Peter H Hwang

Vidya K Rao

Robert S Negrin

Jeffrey J Wine

Carlos Milla

Zachary M Sellers

Tushar J Desai

Matthew H Porteus

Jayakar V Nayak

Affiliations

Soon will be listed here.

Abstract

Modulator agents that restore cystic fibrosis transmembrane conductance regulator (CFTR) function have revolutionized outcomes in cystic fibrosis, an incurable multisystem disease. Barriers exist to modulator use, making local CFTR gene and cell therapies attractive, especially in the respiratory tract. We used CRISPR to gene-correct CFTR in upper airway basal stem cells (UABCs) and show durable local engraftment into recipient murine respiratory epithelium. Interestingly, the human cells recapitulate the organization and differentiation of human sinus epithelium, with little expansion or contraction of the engrafted population over time, while retaining expression of the CFTR transgene. Our results indicate that human airway stem cell transplantation with locoregional restoration of CFTR function is a feasible approach for treating CF and potentially other diseases of the respiratory tract.

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