Journal article
Circular Intermediates of Recombinant Adeno-Associated Virus Have Defined Structural Characteristics Responsible for Long-Term Episomal Persistence in Muscle Tissue
Journal of virology, Vol.72(11), pp.8568-8577
11/1998
DOI: 10.1128/JVI.72.11.8568-8577.1998
PMCID: PMC110267
PMID: 9765395
Abstract
Adeno-associated viral (AAV) vectors have demonstrated great utility for long-term gene expression in muscle tissue. However, the mechanisms by which recombinant AAV (rAAV) genomes persist in muscle tissue remain unclear. Using a recombinant shuttle vector, we have demonstrated that circularized rAAV intermediates impart episomal persistence to rAAV genomes in muscle tissue. The majority of circular intermediates had a consistent head-to-tail configuration consisting of monomer genomes which slowly converted to large multimers of >12 kbp by 80 days postinfection. Importantly, long-term transgene expression was associated with prolonged (80-day) episomal persistence of these circular intermediates. Structural features of these circular intermediates responsible for increased persistence included a DNA element encompassing two viral inverted terminal repeats (ITRs) in a head-to-tail orientation, which confers a 10-fold increase in the stability of DNA following incorporation into plasmid-based vectors and transfection into HeLa cells. These studies suggest that certain structural characteristics of AAV circular intermediates may explain long-term episomal persistence with this vector. Such information may also aid in the development of nonviral gene delivery systems with increased efficiency.
Details
- Title: Subtitle
- Circular Intermediates of Recombinant Adeno-Associated Virus Have Defined Structural Characteristics Responsible for Long-Term Episomal Persistence in Muscle Tissue
- Creators
- Dongsheng Duan - Department of Anatomy and Cell Biology and Department of Internal Medicine, University of Iowa Medical Center, Iowa City, IowaPrerna Sharma - Department of Anatomy and Cell Biology and Department of Internal Medicine, University of Iowa Medical Center, Iowa City, IowaJusan Yang - Department of Anatomy and Cell Biology and Department of Internal Medicine, University of Iowa Medical Center, Iowa City, IowaYongping Yue - Department of Anatomy and Cell Biology and Department of Internal Medicine, University of Iowa Medical Center, Iowa City, IowaLorita Dudus - Department of Anatomy and Cell Biology and Department of Internal Medicine, University of Iowa Medical Center, Iowa City, IowaYulong Zhang - Department of Anatomy and Cell Biology and Department of Internal Medicine, University of Iowa Medical Center, Iowa City, IowaKrishna J Fisher - Department of Anatomy and Cell Biology and Department of Internal Medicine, University of Iowa Medical Center, Iowa City, IowaJohn F Engelhardt - Department of Anatomy and Cell Biology and Department of Internal Medicine, University of Iowa Medical Center, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.72(11), pp.8568-8577
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/JVI.72.11.8568-8577.1998
- PMID
- 9765395
- PMCID
- PMC110267
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Language
- English
- Date published
- 11/1998
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025582402771
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