In vivo kinetics and biodistribution of a HIV-1 DNA vaccine after administration in mice.
In this study we have investigated the pharmacokinetics and tissue distribution of GX-12, a multiple plasmid DNA vaccine for the treatment of HIV-1 infection. Plasmid DNA was rapidly degraded in blood with a half-life of 1.34 min and was no longer detectable at 90 min after intravenous injection in mice. After intramuscular injection, plasmid DNA concentration in the injection site rapidly declined to less than 1% of the initial concentration by 90 min post-injection. However, sub-picogram levels (per mg tissue) were occasionally detected for several days after injection. The relative proportions of the individual plasmids of GX-12 remained relatively constant at the injection site until 90 min post-injection. The concentration of plasmid DNA in tissues other than the injection site peaked at 90 min post-injection and decreased to undetectable levels at 8 h post-injection. The rapid in vivo degradation of GX-12 and absence of persistence in non-target tissues suggest that the risk of potential gene-related toxicities by GX-12 administration, such as expression in non-target tissues, insertional mutagenesis and germline transmission, is minimal.
Kim
Byong-Moon
BM
Research Laboratories, Dong-A Pharm. Co., Ltd., Yongin-si, Kyunggi-do 449-900, Korea. bmkim@donga.co.kr
Lee
Dong-Sop
DS
Choi
Jae-Hoon
JH
Kim
Chae-Young
CY
Son
Miwon
M
Suh
You-Suk
YS
Baek
Kwan-Hyuck
KH
Park
Ki-Seok
KS
Sung
Young-Chul
YC
Kim
Won-Bae
WB
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000493:pharmacokinetics*
D016915:AIDS Vaccines; D019444:Vaccines, DNA