Journal article
Directed evolution of adeno-associated virus to an infectious respiratory virus
Proceedings of the National Academy of Sciences - PNAS, Vol.106(10), pp.3865-3870
03/10/2009
DOI: 10.1073/pnas.0813365106
PMCID: PMC2646629
PMID: 19237554
Abstract
Respiratory viruses evolve to maintain infectivity levels that permit spread yet prevent host and virus extinction, resulting in surprisingly low infection rates. Respiratory viruses harnessed as gene therapy vectors have illustrated this limitation. We used directed evolution in an organotypic human airway model to generate a highly infectious adeno-associated virus. This virus mediated gene transfer more than 100-fold better than parental strains and corrected the cystic fibrosis epithelial Cl
−
transport defect. Thus, under appropriate selective pressures, viruses can evolve to be more infectious than observed in nature, a finding that holds significant implications for designing vectors for gene therapy and for understanding emerging pathogens.
Details
- Title: Subtitle
- Directed evolution of adeno-associated virus to an infectious respiratory virus
- Creators
- Katherine J. D. A Excoffon - Department of Internal Medicine, University of Iowa, 440 EMRB, Iowa City, IA 52241James T Koerber - Departments of Chemical Engineering and Bioengineering and The Helen Willis Neuroscience Institute, University of California, 278 Stanley Hall, Berkeley, CA 94720David D Dickey - Department of Internal Medicine, University of Iowa, 440 EMRB, Iowa City, IA 52241Matthew Murtha - Department of Pediatrics and Children's Research Institute, The Research Institute at Nationwide Children's Hospital and Ohio State University, Columbus, OH 43205; andShaf Keshavjee - Department of Surgery, University of Toronto, Division of Thoracic Surgery, Toronto General Hospital, 200 Elizabeth Street, 9N-946, Toronto, ON, Canada M5G 2C4Brian K Kaspar - Department of Pediatrics and Children's Research Institute, The Research Institute at Nationwide Children's Hospital and Ohio State University, Columbus, OH 43205; andJoseph Zabner - Department of Internal Medicine, University of Iowa, 440 EMRB, Iowa City, IA 52241David V Schaffer - Departments of Chemical Engineering and Bioengineering and The Helen Willis Neuroscience Institute, University of California, 278 Stanley Hall, Berkeley, CA 94720
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.106(10), pp.3865-3870
- DOI
- 10.1073/pnas.0813365106
- PMID
- 19237554
- PMCID
- PMC2646629
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 03/10/2009
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094562902771
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