Enhanced Tropism of Species B1 Adenoviral-Based Vectors for Primary Human Airway Epithelial Cells

Ni Li; Ashley L. Cooney; Wenli Zhang; Anja Ehrhardt; Patrick L. Sinn

doi:10.1016/j.omtm.2019.07.001

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Enhanced Tropism of Species B1 Adenoviral-Based Vectors for Primary Human Airway Epithelial Cells

Journal article

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Enhanced Tropism of Species B1 Adenoviral-Based Vectors for Primary Human Airway Epithelial Cells

Ni Li, Ashley L. Cooney, Wenli Zhang, Anja Ehrhardt and Patrick L. Sinn

Molecular therapy. Methods & clinical development, Vol.14, pp.228-236

09/13/2019

DOI: 10.1016/j.omtm.2019.07.001

PMCID: PMC6690641

PMID: 31417941

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Abstract

Adenoviruses are efficient vehicles for transducing airway epithelial cells. Human adenoviruses (Ads) are classified into seven species termed A–G. Most species use the coxsackie-adenovirus receptor (CAR) as a primary cellular receptor. Ad group B is notable because it is further divided into groups B1 and B2 and its members use CD46 or desmoglein 2 (DSG2) as cellular receptors. To date, human Ad types 2 and 5 have been the predominant choices for preclinical and clinical trials using Ad-based viral vectors in the airways. In this study, we screened 14 Ad types representing species C, B1, B2, D, and E. Using well-differentiated primary cultures of human airway epithelial cells (HAEs), we examined transduction efficiency. Based on GFP or nanoluciferase expression, multiple Ad types transduced HAEs as well as or better than Ad5. Ad3, Ad21, and Ad14 belong to species B and had notable transduction properties. We further examined the transduction properties of conditionally reprogrammed airway basal cells and primary basal cells from human lung donors. Again, the transduction efficiency of species B members outperformed the other types. These data suggest that adenoviral vectors based on species B transduce fully differentiated epithelial cells and progenitor cells in the human airways better than Ad5.

CD46

coxsackie-adenovirus receptor

desmoglein 2

gene therapy

lung gene transfer

respiratory system

Details

Title: Subtitle: Enhanced Tropism of Species B1 Adenoviral-Based Vectors for Primary Human Airway Epithelial Cells
Creators: Ni Li - University of Iowa
Ashley L. Cooney - University of Iowa
Wenli Zhang - Witten/Herdecke University
Anja Ehrhardt - Witten/Herdecke University
Patrick L. Sinn - University of Iowa
Resource Type: Journal article
Publication Details: Molecular therapy. Methods & clinical development, Vol.14, pp.228-236
DOI: 10.1016/j.omtm.2019.07.001
PMID: 31417941
PMCID: PMC6690641
NLM abbreviation: Mol Ther Methods Clin Dev
ISSN: 2329-0501
eISSN: 2329-0501
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: NIH, award: NIH P01 HL-51670, NIH P01 HL-091842, NIH R01 HL-133089, NIH R01 HL-105821; name: Center for Gene Therapy of Cystic Fibrosis, award: NIH P30 DK-054759; DOI: 10.13039/100000897, name: Cystic Fibrosis Foundation, award: SINN15XX0
Language: English
Date published: 09/13/2019
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics
Record Identifier: 9984297437502771

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