NDLI: Decline in Exogenous Gene Expression in Primate Brain Following Intravenous Administration Is Due to Plasmid Degradation

Content Provider	Springer Nature Link
Author	Chu, Chun Zhang, Yun Boado, Ruben J. Pardridge, William M.
Copyright Year	2006
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 receptor.The present studies measure the rate of decay of luciferase gene expression in the Rhesus monkey with luciferase enzyme assays, Southern blotting, and real-time polymerase chain reaction.Luciferase enzyme activity in frontal cortex, cerebellum, and liver decays with a t$_{1/2}$ of 2.1 ± 0.1, 2.6 ± 0.2, and 1.7 ± 0.01 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 real-time polymerase chain reaction, and decayed with t$_{1/2}$ of 1.3 ± 0.3 and 2.7 ± 0.5 days, respectively.The maximal concentration of luciferase plasmid DNA in Rhesus monkey brain was 3–4 molecules/cell following an i.v. 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.
Starting Page	1586
Ending Page	1590
Page Count	5
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	23
Issue Number	7
e-ISSN	1573904X
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-06-21
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	insulin receptor luciferase nonviral gene transfer real-time PCR Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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