Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholesterol clearance in normal mice

Joachim Herz, Robert D. Gerard

Research output: Contribution to journalArticlepeer-review

493 Scopus citations

Abstract

We have explored the use of adenovirus-mediated gene transfer to transiently elicit production of low density lipoprotein (LDL) receptors in mice. A recombinant adenovirus carrying the human LDL receptor cDNA restored LDL receptor function in receptor-deficient cultured cells. Intravenous injection of recombinant virus acutely lowered plasma cholesterol levels and increased the rate of 125I-labeled LDL clearance from the circulation in normal mice. At 4 days after virus injection, the t1/2 of plasma LDL was reduced up to 10-fold. An estimated 90% of the parenchymal cells in liver expressed the adenovirus-transferred genes as judged by immunofluorescence of LDL receptors or by β-galactosidase staining. These results demonstrate that adenovirus-mediated transfer of the LDL receptor gene provides an efficient way of augmenting LDL receptor gene function in the liver over the short term.

Original languageEnglish (US)
Pages (from-to)2812-2816
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number7
DOIs
StatePublished - Apr 1 1993

ASJC Scopus subject areas

  • General

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