Abstract:
:Lipoproteins are emulsion particles that consist of lipids and apolipoproteins. Their natural function is to transport lipids and/or cholesterol to different tissues. We have taken advantage of the hydrophobic interior of these natural emulsions to solubilize DNA. Negatively charged DNA was first complexed with cationic lipids containing a quaternary amine head group. The resulting hydrophobic complex was extracted by chloroform and then incorporated into reconstituted chylomicron remnant particles ( approximately 100 nm in diameter) with an efficiency approximately 65%. When injected into the portal vein of mice, there were approximately 5 ng of a transgene product (luciferase) produced per mg of liver protein per 100 microg injected DNA. This level of transgene expression was approximately 100-fold higher than that of mice injected with naked DNA. However, such a high expression was not found after tail vein injection. Histochemical examination revealed that a large number of parenchymal cells and other types of cells in the liver expressed the transgene. Gene expression in the liver increased with increasing injected dose, and was nearly saturated with 50 microg DNA. At this dose, the expression was kept at high level in the liver for 2 days and then gradually reduced and almost disappeared by 7 days. However, by additional injection at day 7, gene expression in the liver was completely restored. By injection of plasmid DNA encoding human alpha1-antitrypsin, significant concentrations of hAAT were detected in the serum of injected animals. This is the first nonviral vector that resembles a natural lipoprotein carrier.
journal_name
Proc Natl Acad Sci U S Aauthors
Hara T,Tan Y,Huang Ldoi
10.1073/pnas.94.26.14547subject
Has Abstractpub_date
1997-12-23 00:00:00pages
14547-52issue
26eissn
0027-8424issn
1091-6490journal_volume
94pub_type
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