학술논문
A sensitive noninvasive method for monitoring successful liver-directed gene transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic rabbits in vivo.
Document Type
Article
Author
Source
Subject
*TRANSGENE expression
*GENE therapy
*HYPERLIPIDEMIA
*LIPID metabolism disorders
*RABBITS
*THERAPEUTICS
*
*
*
*
*
Language
ISSN
0969-7128
Abstract
Noninvasive tools to quantitate transgene expression directly are a prerequisite for clinical gene therapy. We established a method to determine location, magnitude, and duration of low-densitiy lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected 111In-labeled LDL using a scintillation camera. Liver-specific tracer uptake was calculated by normalizing the counts measured over the liver to counts measured over the heart that represent the circulating blood pool of the tracer (liver/heart (L/H) ratio). Our results indicate that the optimal time point for transgene imaging is 4?h after the tracer injection. Compared with control virus-injected rabbits, animals treated with the LDLR-expressing adenovirus showed seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold higher L/H ratios on day 30. This imaging method might be a useful strategy to obtain reliable data on functional transgene expression in clinical gene therapy trials of familial hypercholesterolemia.Gene Therapy (2004) 11, 574-580. doi:10.1038/sj.gt.3302206 Published online 15 January 2004 [ABSTRACT FROM AUTHOR]