A Hybrid Adenoviral Vector System Achieves Efficient Long-Term Gene Expression in the Liver via piggyBac Transposition

Ryan P Smith; Jesse D Riordan; Charlotte R Feddersen; Adam J Dupuy

doi:10.1089/hum.2014.123

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A Hybrid Adenoviral Vector System Achieves Efficient Long-Term Gene Expression in the Liver via piggyBac Transposition

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A Hybrid Adenoviral Vector System Achieves Efficient Long-Term Gene Expression in the Liver via piggyBac Transposition

Ryan P Smith, Jesse D Riordan, Charlotte R Feddersen and Adam J Dupuy

Human gene therapy, Vol.26(6), pp.377-385

06/2015

DOI: 10.1089/hum.2014.123

PMCID: PMC4492551

PMID: 25808258

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Abstract

Much research has gone into the development of hybrid gene delivery systems that combine the broad tropism and efficient transduction of adenoviral vectors with the ability to achieve stable expression of cargo genes. In addition to gene therapy applications, such a system has considerable advantages for studies of gene function in vivo, permitting fine-tuned genetic manipulation with higher throughput than can be achieved using standard transgenic and DNA targeting techniques. Existing strategies are limited, however, by low integration efficiencies, small cargo capacity, and/or a dependence on target cell division. The utility of this approach could be enhanced by a system that provides all of the following: (1) efficient delivery, (2) stable expression in a high percentage of target cells (whether mitotic or not), (3) large cargo capacity, (4) flexibility to use with a wide range of additional experimental conditions, and (5) simple experimental technique. Here we report the initial characterization of a hybrid system that meets these criteria by utilizing piggyBac (PB) transposition to achieve genomic integration from adenoviral vectors. We demonstrate stable expression of an adenovirus (Ad)-PB-delivered reporter gene in ∼20-40% of hepatocytes following standard tail vein injection. Its high efficiency and flexibility relative to existing hybrid adenoviral gene delivery approaches indicate a considerable potential utility of the Ad-PB system for therapeutic gene delivery and in vivo studies of gene function.

Cell Line

Gene Transfer Techniques

Animals

Cells, Cultured

Gene Expression Regulation

Adenoviridae - genetics

Liver - physiology

Genetic Vectors

Mice, Inbred Strains

Transgenes

DNA Transposable Elements

Details

Title: Subtitle: A Hybrid Adenoviral Vector System Achieves Efficient Long-Term Gene Expression in the Liver via piggyBac Transposition
Creators: Ryan P Smith - Department of Anatomy and Cell Biology, Roy J. & Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IA 52242
Jesse D Riordan - Department of Anatomy and Cell Biology, Roy J. & Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IA 52242
Charlotte R Feddersen - Department of Anatomy and Cell Biology, Roy J. & Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IA 52242
Adam J Dupuy - Department of Anatomy and Cell Biology, Roy J. & Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IA 52242
Resource Type: Journal article
Publication Details: Human gene therapy, Vol.26(6), pp.377-385
DOI: 10.1089/hum.2014.123
PMID: 25808258
PMCID: PMC4492551
NLM abbreviation: Hum Gene Ther
ISSN: 1043-0342
eISSN: 1557-7422
Publisher: United States
Grant note: T32 GM067795 / NIGMS NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 06/2015
Academic Unit: Anatomy and Cell Biology; Pathology
Record Identifier: 9984025358602771

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