Systemic administration of TerplexDNA system: Pharmacokinetics and gene expression

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.