Journal article
Hybrid Nonviral/Viral Vector Systems for Improved piggyBac DNA Transposon In Vivo Delivery
Molecular therapy, Vol.23(4), pp.667-674
04/2015
DOI: 10.1038/mt.2014.254
PMCID: PMC4395777
PMID: 25557623
Abstract
The DNA transposon
piggyBac
is a potential therapeutic agent for multiple genetic diseases such as cystic fibrosis (CF). Recombinant
piggyBac
transposon and transposase are typically codelivered by plasmid transfection; however, plasmid delivery is inefficient in somatic cells
in vivo
and is a barrier to the therapeutic application of transposon-based vector systems. Here, we investigate the potential for hybrid
piggyBac
/viral vectors to transduce cells and support transposase-mediated genomic integration of the transposon. We tested both adenovirus (Ad) and adeno-associated virus (AAV) as transposon delivery vehicles. An Ad vector expressing hyperactive insect
piggyBac
transposase (iPB7) was codelivered. We show transposase-dependent transposition activity and mapped integrations in mammalian cells
in vitro
and
in vivo
from each viral vector platform. We also demonstrate efficient and persistent transgene expression following nasal delivery of
piggyBac
/viral vectors to mice. Furthermore, using
piggyBac
/Ad expressing Cystic Fibrosis transmembrane Conductance Regulator (CFTR), we show persistent correction of chloride current in well-differentiated primary cultures of human airway epithelial cells derived from CF patients. Combining the emerging technologies of DNA transposon-based vectors with well-studied adenoviral and AAV delivery provides new tools for
in vivo
gene transfer and presents an exciting opportunity to increase the delivery efficiency for therapeutic genes such as CFTR.
Details
- Title: Subtitle
- Hybrid Nonviral/Viral Vector Systems for Improved piggyBac DNA Transposon In Vivo Delivery
- Creators
- Ashley L Cooney - , Iowa City, IowaBrajesh K Singh - , Iowa City, IowaPatrick L Sinn - , Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular therapy, Vol.23(4), pp.667-674
- Publisher
- Nature Publishing Group
- DOI
- 10.1038/mt.2014.254
- PMID
- 25557623
- PMCID
- PMC4395777
- ISSN
- 1525-0016
- eISSN
- 1525-0024
- Language
- English
- Date published
- 04/2015
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics
- Record Identifier
- 9984093607702771
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