How can gene editing of human pluripotent stem cells help understand the effect of genetics on respiratory diseases?

Le résumé fourni par la source

Advances in functional genomics are leading the expansion of our knowledge on the role of genetics in respiratory conditions. However, we still need classical genetics to ultimately confirm the role of specific genes in disease. Current approaches to identify gene9s roles are either not representative of the disease phenotype or highly time consuming, thus, not feasible in many cases. We aimed to develop an efficient method to genetically manipulate human pluripotent stem cells (hPSCs), which followed by tissue specific differentiation, would speed up the process of generating mutation customised disease relevant tissue specific platforms to complete our understanding of the role of genetics in lung diseases. Using cystic fibrosis (CF) as an example of monogenic disease and exploring hPSC culture conditions and manipulation, we introduced the most common CF mutation, ΔF508, into the CFTR gene, using TALENs into hPSCs. We also corrected the W1282X mutation using CRISPR-Cas9 in human-induced PSCs. This simple method achieved heterozygous and homozygous gene-edited hPSCs with ≤10% efficiency in 3–6 weeks, instead of months. The developed method offers the solution to generate patient derived or mutation customised models derived from hPSCs in a timely manner to assess the function of genes identified by functional genomic approaches. Better integrating gene editing technologies of hPSCs as ultimate step to validate disease associated genes will increase our understanding of genetic determinants of disease development early and later in life, will accelerate the identification of new drug targets for respiratory diseases and will improve precision medicine.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.