Purpose. The aim of this study is to extend our previous studies to investi
gate the TerplexDNA synthetic gene carrier system in pharmacokinetics, biod
istribution, and gene expression in major organs after systemic administrat
ion.
Methods. The stability of the TerplexDNA system was analyzed in vitro with
a serum incubation assay. The TerplexDNA PK/PD studies were conducted by qu
antitation of Terplex/radiolabeled DNA [CTP alpha-P-32] complexes after rat
-tail vein injection. The effect of the TerplexDNA system on gene expressio
n in mouse major organs was analyzed by measuring luciferase activities aft
er systemic administration.
Results. The TerplexDNA gene carrier showed significantly longer retention
in the vascular space than naked plasmid DNA alone. At early time points (1
h postvenous injection), the lung was the major organ of the TerplexDNA di
stribution, followed by the liver as a major distribution organ at later ti
me points (24 h postinjection). The major organs of transgene expression af
ter intravenous injection were the liver and heart.
Conclusion. The TerplexDNA system has the potential for in vivo application
s due to its higher bioavailability of plasmid DNA in the tissues, and due
to its organ specific distribution.