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Cited by 59Virus-based gene therapy researchCystic Fibrosis Research AdvancesRNA Interference and Gene Delivery

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

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Marquez Loza, Laura I., Yuen, Eric C., McCray, Paul B.·2019·Genes
DOI 10.3390/genes10030218PMC PMC6471883
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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.

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  • Genetic correction does not require continuous expression of the nuclease, thereby bypassing the need for a stable transgene expression.

    “Furthermore, genetic correction does not require continuous expression of the nuclease thereby bypassing the need for a stable transgene expression58.”

    From Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing (2019) · cites this paper as [58]

    The Abstract describes lentiviral vectors providing long-term transgene expression, but does not address whether genetic correction requires continuous nuclease expression. Searches for nuclease, CRISPR, and transient genome editing found no passage in our copy that addresses that distinction. Page numbers are unavailable in the indexed copy. (LLM, conf=0.74)

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Cited by

Sorted by citations

Authors
Marquez Loza, L. I., Yuen, E. C., & McCray, P. B.
Affiliations
  • Stead Family Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA
  • Talee Bio, 3001 Market Street, Suite 140, Philadelphia, PA 19104, USA
  • University of Iowa (US)
Corresponding author
McCray, Paul B.
ORCID
McCray, Paul B.
Venue
Genes
Publisher
MDPI AG
Published
2019-03-14
Volume
10
Issue
3
Pages
218
ISSN
2073-4425 (ISSN-L)
DOI
10.3390/genes10030218
PMC
PMC6471883
OpenAlex
W2922315004
Cited by
59
References
10
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 12 · 2021: 11 · 2020: 17 · 2019: 4
FWCI
1.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Genes (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Center for Gene Therapy, University of Iowa (NIH P30 DK 054759)
  • National Institutes of Health (NIH P01 HL-51670, NIH P01 HL-091842, NIH R01 HL-133089, NIH R01 HL-105821, NIH R44 HL-139218, NIH T32GM007337)
  • Cystic Fibrosis Foundation (511141)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
cystic fibrosis, lentiviral vectors, CFTR gene therapy, nonsense mutation, airway epithelium, insertional mutagenesis, vector safety, immunogenicity, CFTR expression
MeSH terms
Animals, Cystic Fibrosis, Genetic Vectors, Humans, Genetic Therapy, Lentivirus, Cystic Fibrosis Transmembrane Conductance Regulator

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