Gene Expression of GX-12, a New Naked DNA Vaccine for HIV Infection, in Reproductive Organs

  • Park, Seul-Min (Research Laboratories, DongA Pharmaceutical Co. Ltd.) ;
  • Kang, Kyung-Koo (Research Laboratories, DongA Pharmaceutical Co. Ltd.) ;
  • Lee, Dong-Sup (Research Laboratories, DongA Pharmaceutical Co. Ltd.) ;
  • Park, Jae-Hoon (Research Laboratories, DongA Pharmaceutical Co. Ltd.) ;
  • Sohn, Yong-Sung (Research Laboratories, DongA Pharmaceutical Co. Ltd.) ;
  • Kim, Chae-Young (Research Laboratories, DongA Pharmaceutical Co. Ltd.) ;
  • Kim, Byung-Moon (Research Laboratories, DongA Pharmaceutical Co. Ltd.) ;
  • Kim, Won-Bae (Research Laboratories, DongA Pharmaceutical Co. Ltd.)
  • Published : 2003.03.01

Abstract

GX-12 is a naked DNA vaccine developed by the DongA Pharmaceutical Co. Ltd. and Genexine for the treatment of HIV infection. This study was peformed to evaluate the biodistribution and expression of GX-12 mRNA in gonadal tissues, and to investigate the histopathological changes after the repeated intramuscular injection. GX-12 (400 $\mu\textrm{g}$/head) was injected into the left anterior tibialis once a week for four weeks. On day 1, 5, 15, 30 and 45 after the final administration, gonadal tissues (testes, epididymis, seminal vesicles, penis, prostate glands, ovaries, vagina, uterus) and the injection site (muscle) were harvested and examined for the expression of mRNA by RT-PCR. In addition, histopathological examination was peformed at each time point. At the injection site, mRNA expression of GX-12 was detected only at early time points (1 ~ 15 days after injection) but not thereafter. However, in gonadal tissues, mRNA expression was not identified at all time points both in male and female rats. There were no histopathological changes in all reproductive organs and muscle. Based on these results, it is unlikely that the plasmid DNAs of GX-12 was distributed to- and expressed in gonadal tissues, suggesting that the chance of germline integration and transmission is negligible.

Keywords

References

  1. DDT v.7 The past, present and future of HIV-vaccine development: a critical view Bojak,A.;Deml,L.;Wagner,R. https://doi.org/10.1016/S1359-6446(01)02081-5
  2. Docket No. 96N-0400 Points to consider on plasmid DNA vaccines for preventive infectious disease indications Food and Drug Administration
  3. Notification No. 2000-61 Regulatory Guidelines for gene therapy Korea Food and Drug Administration
  4. Intervirol v.43 Plasmid DNA vaccine: Investigation of integration into host cellular DNA following intramuscular injection in mice Ledwith,B.J.;Manamm S,;Troilo,P.J.;Barnum,A.B.;Pauley,C.J.;Griffiths,ll T.G.;Harper,L.B.;Beare,C.M.;Bagdon,W.J.;Nichols,W.W. https://doi.org/10.1159/000053993
  5. Intervirol v.43 Plasmid DNA vaccines: Tissue distribution and effects of DNA sequence, adjuvants and delivery method on integration into host DNA Manam,S.;Ledwith,B.J.;;Barnum,A.B.;Troilo,P.J.;Pauley,C.J.;Harper,L.B.;Griffiths,ll T.G.;Niu,Z.;Denisova,L.;Follmer,T.T.;Pacchione,S.J.;Wang,Z.;Beare,C.M.;Bagdon,W.J.;Nichols,W.W. https://doi.org/10.1159/000053994
  6. Vaccine v.20 Rational developmen of ptophylactic HIV vaccines based on structural and regulatory proteins Mooij,P.;Heeney,J.L. https://doi.org/10.1016/S0264-410X(01)00373-5
  7. A laboratory manual (2nd ed.) Molecular cloning Sambrook,J.;Frisch,E.F.;Maniatis,T.