Functional Gene Correction for Cystic Fibrosis in Lung Epithelial Cells Generated from Patient iPSCs.

Abstract:

:Lung disease is a major cause of death in the United States, with current therapeutic approaches serving only to manage symptoms. The most common chronic and life-threatening genetic disease of the lung is cystic fibrosis (CF) caused by mutations in the cystic fibrosis transmembrane regulator (CFTR). We have generated induced pluripotent stem cells (iPSCs) from CF patients carrying a homozygous deletion of F508 in the CFTR gene, which results in defective processing of CFTR to the cell membrane. This mutation was precisely corrected using CRISPR to target corrective sequences to the endogenous CFTR genomic locus, in combination with a completely excisable selection system, which significantly improved the efficiency of this correction. The corrected iPSCs were subsequently differentiated to mature airway epithelial cells where recovery of normal CFTR expression and function was demonstrated. This isogenic iPSC-based model system for CF could be adapted for the development of new therapeutic approaches.

journal_name

Cell Rep

journal_title

Cell reports

authors

Firth AL,Menon T,Parker GS,Qualls SJ,Lewis BM,Ke E,Dargitz CT,Wright R,Khanna A,Gage FH,Verma IM

doi

10.1016/j.celrep.2015.07.062

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

1385-90

issue

9

issn

2211-1247

pii

S2211-1247(15)00852-9

journal_volume

12

pub_type

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