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• W1978135902 abstract "Background To properly study gene expression in vivo, often long-term expression is desired. Previous studies using plasmid DNA (pDNA) vectors have typically resulted in short-term expression. Here, we evaluated combinations of the albumin promoter with different enhancers and untranslated regions for liver-specific expression in mice. Methods A series of pDNA secreted alkaline phosphatase (SEAP) reporter gene expression vectors was constructed using the albumin promoter and various other expression cassette elements. Each was evaluated for level and duration of SEAP expression in mice following hydrodynamic tail vein delivery. Results Sustained liver expression was obtained from vectors combining the albumin promoter with an albumin 3′ untranslated region (3′UTR). The level of expression was increased by inclusion of enhancers and a 5′ intron. The optimal expression vector consisted of the albumin promoter combined with an α-fetoprotein MERII enhancer, 5′ intron from the factor IX gene, and the 3′UTR from the albumin gene including intron 14. With this vector, SEAP reporter gene expression levels remained high for 1 year, at levels comparable to those obtained from the cytomegalovirus (CMV) promoter on day 1. Expression of human apolipoprotein E3 (hApoE) in ApoE knockout mice provided a dose-dependent correction of their hypercholesterolemia. Conclusions Liver-specific sustained transgene expression can be obtained at very high levels from optimized pDNA vectors, without the use of integration systems. Such vectors will further facilitate biological studies of genes in vivo and may find application in gene therapy. Copyright © 2008 John Wiley & Sons, Ltd." @default.
• W1978135902 created "2016-06-24" @default.
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• W1978135902 date "2008-01-01" @default.
• W1978135902 modified "2023-09-27" @default.
• W1978135902 title "Sustained liver-specific transgene expression from the albumin promoter in mice following hydrodynamic plasmid DNA delivery" @default.
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• W1978135902 doi "https://doi.org/10.1002/jgm.1179" @default.
• W1978135902 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18330848" @default.
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