当前位置： SCI文献检索 > JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION期刊下所有文献 > Gene transfer to the gastrointestinal tract after peroral administration of recombinant adeno-associated virus type 2 vectors.

Gene transfer to the gastrointestinal tract after peroral administration of recombinant adeno-associated virus type 2 vectors.

Abstract：

OBJECTIVES:The transfer of exogenous genetic material to cells within the gastrointestinal (GI) tract has many potential therapeutic applications. An attractive feature of the GI tract for gene transfer is its accessibility through the orogastric route. In this study, we evaluated the stability of recombinant adeno-associated virus type 2 (rAAV2) vectors within the GI tract and whether rAAV2-mediated gene transfer could be increased through manipulation of the intraluminal environment. METHODS:The stability of rAAV2 vectors carrying beta-galactosidase and enhanced green fluorescence protein transgenes was determined in the presence of hydrochloric acid, pepsin, trypsin, chymotrypsin gastric fluid and intestinal fluid and after in vivo administration. For in vivo experiments, the rAAV2 vector carrying the beta-galactosidase transgene was administered perorally to FVB/NJ mice. Groups of mice received the vector alone or in combination with sodium bicarbonate and aprotinin. Gene transfer to the stomach and small intestine was evaluated by polymerase chain reaction and histochemical assays. RESULTS:The stability of rAAV2 was reduced by hydrochloric acid, trypsin, chymotrypsin, gastric fluid and intestinal fluid. The vector was not stable within the lumen of the GI tract. Gastric acid neutralization with sodium bicarbonate and protease inhibition with aprotinin increased the in vivo stability of the vector and the level of gene transfer to the stomach and all regions of the small bowel. In both groups of mice (vector alone and vector plus sodium bicarbonate and aprotinin), transgene-derived protein expression (beta-galactosidase) was below the level of detection of the histochemical assay. CONCLUSIONS:Recombinant AAV2 are adversely affected by physiological conditions within the proximal GI tract. Gastric acid neutralization and inhibition of intestinal protease activity improved rAAV2 stability and increased the level of gene transfer within the GI tract. Despite these changes, transduction of the GI tract after peroral rAAV2 administration remained low.

journal_name

J Pediatr Gastroenterol Nutr

journal_title

Journal of pediatric gastroenterology and nutrition

authors

Shao G,Greathouse K,Huang Q,Wang CM,Sferra TJ

doi

10.1097/01.mpg.0000228118.59853.ba

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

168-79

issue

eissn

0277-2116

issn

1536-4801

pii

00005176-200608000-00006

journal_volume

pub_type

杂志文章

在线工具

Gene transfer to the gastrointestinal tract after peroral administration of recombinant adeno-associated virus type 2 vectors.