Simian immunodeficiency virus-based lentivirus vector for retinal gene transfer: A preclinical safety study in adult rats

Y. Ikeda, Y. Goto, Y. Yonemitsu, M. Miyazaki, T. Sakamoto, T. Ishibashi, T. Tabata, Y. Ueda, M. Hasegawa, S. Tobimatsu, K. Sueishi

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Although lentivirus vectors hold promise for ocular gene therapy, they also have potential safety issues, particularly in the case of the current human immunodeficiency virus-based vectors. We recently developed a novel lentivirus vector derived from the nonpathogenic simian immunodeficiency virus from African green monkeys (SIVagm) to minimize these potentials. In this preclinical study, we evaluated whether SIV vector could be efficiently and safely applicable to retinal gene transfer by assessing the transgene expression, retinal function and histology over a 1-year period following subretinal injection in adult rats. The functional assessment via electroretinogram after both titers of SIV-lacZ (2.5 × 107 or 2.5 × 108 transducing units/ml) injection revealed both the dark and light adaptations to soon be impaired, in a dose-dependent manner, after a buffer injection as well, and all of them recovered to the control range by day 30. In both titers tested, the retinas demonstrated a frequent transgene expression mainly in the retinal pigment epithelium; however, the other retinal cells rarely expressed the transgene. Retinas exposed to a low titer virus showed no significant inflammatory reaction throughout the observation period, and also maintained the transgene expression over a 1-year period. In the retinas exposed to a high titer virus, however, mononuclear cell infiltration persisted in the subretinal area, and the retina that corresponded to the injected area finally underwent degeneration by around day 90. No retinal neoplastic lesions could be found in any animals over the 1-year period. We thus propose that SIV-mediated stable gene transfer might be useful for ocular gene transfer, however, more attention should be paid to avoiding complications when administering high titer lentivirus to the retina.

Original languageEnglish
Pages (from-to)1161-1169
Number of pages9
JournalGene Therapy
Issue number14
Publication statusPublished - Jul 2003

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics


Dive into the research topics of 'Simian immunodeficiency virus-based lentivirus vector for retinal gene transfer: A preclinical safety study in adult rats'. Together they form a unique fingerprint.

Cite this