Gene Delivery to Intestinal Epithelial Cells In vitro and In vivo with Recombinant Adeno-Associated Virus Types 1, 2 and 5

Steven Polyak; Cathryn Mah; Stacy Porvasnik; John-David Herlihy; Martha Campbell-Thompson; Barry Byrne; John Valentine

doi:10.1007/s10620-007-9991-1

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Gene Delivery to Intestinal Epithelial Cells In vitro and In vivo with Recombinant Adeno-Associated Virus Types 1, 2 and 5

Journal article

Peer reviewed

Gene Delivery to Intestinal Epithelial Cells In vitro and In vivo with Recombinant Adeno-Associated Virus Types 1, 2 and 5

Steven Polyak, Cathryn Mah, Stacy Porvasnik, John-David Herlihy, Martha Campbell-Thompson, Barry Byrne and John Valentine

Digestive diseases and sciences, Vol.53(5), pp.1261-1270

05/2008

DOI: 10.1007/s10620-007-9991-1

PMCID: PMC3896329

PMID: 17934813

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https://www.ncbi.nlm.nih.gov/pmc/articles/3896329View

Open Access

Abstract

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.

Biochemistry, general

Gene delivery

Adeno-associated virus

Medicine & Public Health

Green fluorescence protein

Hepatology

Gastroenterology

Oncology

Colon

Small intestine

Transplant Surgery

Epithelial

Details

Title: Subtitle: Gene Delivery to Intestinal Epithelial Cells In vitro and In vivo with Recombinant Adeno-Associated Virus Types 1, 2 and 5
Creators: Steven Polyak - Division of Gastroenterology, Department of Medicine University of Florida Gainesville FL 32610 USA
Cathryn Mah - Division of Cellular and Molecular Therapy, Department of Pediatrics University of Florida Gainesville FL 32610 USA
Stacy Porvasnik - Division of Pediatric Cardiology, Department of Pediatrics, Powell Gene Therapy Center University of Florida Gainesville FL 32610 USA
John-David Herlihy - Department of Neuroscience University of Florida Gainesville FL 32610 USA
Martha Campbell-Thompson - Department of Pathology, Immunology and Laboratory Medicine University of Florida Gainesville FL 32610 USA
Barry Byrne - Division of Pediatric Cardiology, Department of Pediatrics, Powell Gene Therapy Center University of Florida Gainesville FL 32610 USA
John Valentine - Division of Gastroenterology, Department of Medicine University of Florida Gainesville FL 32610 USA
Resource Type: Journal article
Publication Details: Digestive diseases and sciences, Vol.53(5), pp.1261-1270
DOI: 10.1007/s10620-007-9991-1
PMID: 17934813
PMCID: PMC3896329
NLM abbreviation: Dig Dis Sci
ISSN: 0163-2116
eISSN: 1573-2568
Publisher: Springer US
Language: English
Date published: 05/2008
Academic Unit: Internal Medicine
Record Identifier: 9984094608602771

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