Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease

Laura I Marquez Loza; Eric C Yuen; Paul B McCray Jr

doi:10.3390/genes10030218

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Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease

Journal article

Open access

Peer reviewed

Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease

Laura I Marquez Loza, Eric C Yuen and Paul B McCray Jr

Genes, Vol.10(3), p.218

03/14/2019

DOI: 10.3390/genes10030218

PMCID: PMC6471883

PMID: 30875857

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Abstract

Despite the continued development of cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs for the treatment of cystic fibrosis (CF), the need for mutation agnostic treatments remains. In a sub-group of CF individuals with mutations that may not respond to modulators, such as those with nonsense mutations, CFTR gene transfer to airway epithelia offers the potential for an effective treatment. Lentiviral vectors are well-suited for this purpose because they transduce nondividing cells, and provide long-term transgene expression. Studies in primary cultures of human CF airway epithelia and CF animal models demonstrate the long-term correction of CF phenotypes and low immunogenicity using lentiviral vectors. Further development of CF gene therapy requires the investigation of optimal CFTR expression in the airways. Lentiviral vectors with improved safety features have minimized insertional mutagenesis safety concerns raised in early clinical trials for severe combined immunodeficiency using γ-retroviral vectors. Recent clinical trials using improved lentiviral vectors support the feasibility and safety of lentiviral gene therapy for monogenetic diseases. While work remains to be done before CF gene therapy reaches the bedside, recent advances in lentiviral vector development reviewed here are encouraging and suggest it could be tested in clinical studies in the near future.

Animals

Cystic Fibrosis - prevention & control

Cystic Fibrosis - therapy

Cystic Fibrosis Transmembrane Conductance Regulator - genetics

Cystic Fibrosis Transmembrane Conductance Regulator - metabolism

Genetic Therapy - methods

Genetic Vectors - genetics

Humans

Lentivirus - genetics

Details

Title: Subtitle: Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease
Creators: Laura I Marquez Loza - Pappajohn Biomedical Institute and the Center for Gene Therapy, The University of Iowa, Iowa City, IA 52242, USA. laura-marquezloza@uiowa.edu
Eric C Yuen
Paul B McCray Jr - Stead Family Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA. paul-mccray@uiowa.edu
Resource Type: Journal article
Publication Details: Genes, Vol.10(3), p.218
DOI: 10.3390/genes10030218
PMID: 30875857
PMCID: PMC6471883
NLM abbreviation: Genes (Basel)
ISSN: 2073-4425
eISSN: 2073-4425
Grant note: P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS R01 HL105821 / NHLBI NIH HHS T32 GM007337 / NIGMS NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS R44 HL139218 / NHLBI NIH HHS R01 HL133089 / NHLBI NIH HHS
Language: English
Date published: 03/14/2019
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984297430102771

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