Authors: Chun Chu Yun Zhang Ruben J Boado William M Pardridge
Publish Date: 2006/06/21
Volume: 23, Issue: 7, Pages: 1586-1590
Abstract
Nonviral gene transfer to the brain of adult Rhesus monkeys is possible with a single intravenous administration of plasmid DNA that is encapsulated in the interior of pegylated immunoliposomes which are targeted across membrane barriers in vivo with a monoclonal antibody to the human insulin receptorLuciferase enzyme activity in frontal cortex cerebellum and liver decays with a t1/2 of 21 ± 01 26 ± 02 and 17 ± 001 days respectively Luciferase plasmid in brain and liver was detectable by Southern blotting at 2 days but not at 7 or 14 days The concentration of luciferase plasmid DNA in brain and liver was measured by realtime polymerase chain reaction and decayed with t1/2 of 13 ± 03 and 27 ± 05 days respectivelyThe maximal concentration of luciferase plasmid DNA in Rhesus monkey brain was 3–4 molecules/cell following an iv administration of 12 μg/kg pegylated immunoliposome encapsulated plasmid DNA These results demonstrate that the rate of loss of exogenous gene expression in the primate in vivo correlates with the rate of DNA degradation of the exogenous plasmid DNA
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