Document Detail


Gene delivery to intestinal epithelial cells in vitro and in vivo with recombinant adeno-associated virus types 1, 2 and 5.
MedLine Citation:
PMID:  17934813     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Intestinal disorders such as inflammatory bowel disease (IBD) result in chronic illness requiring lifelong therapy. Our aim was to evaluate the efficacy of recombinant adeno-associated virus (AAV) vector-mediated gene delivery to intestinal epithelial cells in vitro and in vivo. Human colon epithelial cell lines and colon biopsies were transduced using AAV pseudotypes 2/1, 2/2, and 2/5 encoding green fluorescence protein (GFP). Mice were administered the same vectors through oral, enema, intraperitoneal (IP) injection and superior mesenteric artery (SMA) injection routes. Tropism and efficiency were determined by microscopy, flow cytometry, immunohistochemistry and PCR. Caco2 cells were more permissive to AAV transduction. Human colon epithelial cells in organ culture were more effectively transduced by AAV2/2. SMA injection provided the most effective means of vector gene transfer to small intestine and colonic epithelial cells in vivo. Transgene detection 80 days post AAV treatment suggests transduction of crypt progenitor cells. This study shows the feasibility of AAV-mediated intestinal gene delivery, applicable for the investigation of IBD pathogenesis and novel therapeutic options, but also revealed the need for further studies to identify more efficient pseudotypes.
Authors:
Steven Polyak; Cathryn Mah; Stacy Porvasnik; John-David Herlihy; Martha Campbell-Thompson; Barry J Byrne; John F Valentine
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-10-13
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  53     ISSN:  0163-2116     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-10     Completed Date:  2008-06-17     Revised Date:  2014-01-24    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1261-70     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Dependovirus / genetics*
Feasibility Studies
Flow Cytometry
Gene Transfer Techniques*
Genetic Therapy / methods*
Genetic Vectors / administration & dosage*
Immunohistochemistry
Intestinal Mucosa / metabolism*
Mice
Polymerase Chain Reaction
Transgenes
Grant Support
ID/Acronym/Agency:
T32 DK 60443/DK/NIDDK NIH HHS; T32 DK060443/DK/NIDDK NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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