Abstract:
:Cystic fibrosis (CF) is a multiorgan recessive genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Gene therapy efforts have focused on treating the lung, since it manifests the most significant life-threatening disease. Over two decades have past since the first CF lung gene therapy trials and significant advances in the therapeutic implementation of pharmacologic CFTR modulators have renewed the field's focus on developing gene therapies for the 10% of CF patients these modulators cannot help. This review summarizes recent progress made in developing vectors for airway transduction and CF animal models required for understanding the relevant cellular targets in the lung and testing the efficacy of gene therapy approaches. We also highlight future opportunities in emerging gene editing strategies that may offer advantages for treating diseases like CF where the gene target is highly regulated at the cellular level. The outcomes of CF lung gene therapy trials will likely inform productive paths toward gene therapy for other complex genetic disorders, while also advancing treatments for all CF patients.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Yan Z,McCray PB Jr,Engelhardt JFdoi
10.1093/hmg/ddz139subject
Has Abstractpub_date
2019-10-01 00:00:00pages
R88-R94issue
R1eissn
0964-6906issn
1460-2083pii
5537028journal_volume
28pub_type
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