Biodistribution and general safety of a naked DNA plasmid, GTU-MultiHIV, in a rat, using a quantitative PCR method.

We studied the general safety, biodistribution and persistence of a naked DNA plasmid in a rat model using intramuscular, intradermal and intravenous routes of administration. Clinical signs were followed up throughout the study and at the necropsy. Tissue samples were collected at the necropsy at 2, 14 and 28 days after injection of 200 microg of plasmid DNA and analysed with validated quantitative polymerase chain reaction (QPCR). The plasmid (GTU-MultiHIV) was shown to be well tolerated and no clinical observations related to the vaccine were found. Within 2 days after the intramuscular and intradermal injections, the plasmid could be detected in the lymph nodes and also at 14 days in a few test animals. The quantitative PCR analysis indicated that in positive lymph nodes one of 15-213 dendritic cells could be carrying the plasmid. No plasmid was detected in gonads or brain samples in any of the study groups. In intramuscular and intradermal administration, low amounts of the plasmid DNA persisted at the injection site 28 days after the injection, whereas a complete clearance with intravenous route was observed already at 14 days. The results show that the GTU-MultiHIV plasmid is safe and suitable for human clinical trials.