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Prime editing-mediated correction of the <i>CFTR</i> W1282X mutation in iPSCs and derived airway epithelial cells

by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao

A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.

Assessing the role of combination of stem cell and light‐based treatments on skin wound repair: A meta‐analysis

Abstract

The meta-analysis aims to evaluate and compare the impact of the combination of stem cells (SCs) and light-based treatments (LBTs) on skin wound (SW) repair. Examinations comparing SCs to LBT with SCs for SW repair was among the meta-analysis from various languages that met the inclusion criteria. Using continuous random-effect models, the results of these investigations were examined, and the mean difference (MD) with 95% confidence intervals was computed (CIs). Seven examinations from 2012 to 2022 were recruited for the current analysis including 106 animals with SWs. Photobiomodulation therapy (PBT) plus SCs had a significantly higher wound closure rate (WCR) (MD, 9.08; 95% CI, 5.55–12.61, p < 0.001) compared to SCs in animals with SWs. However, no significant difference was found between PBT plus SCs and SCs on wound tensile strength (WTS) (MD, 2.01; 95% CI, −0.42 to 4.44, p = 0.10) in animals with SWs. The examined data revealed that PBT plus SCs had a significantly higher WCR, however, no significant difference was found in WTS compared to SCs in animals with SWs. Nevertheless, caution should be exercised while interacting with its values since all the chosen examinations were found with a low sample size and a low number of examinations were found for the comparisons studied for the meta-analysis.

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