Acute toxicity study of a simian immunodeficiency virus-based lentiviral vector for retinal gene transfer in nonhuman primates

Yasuhiro Ikeda, Yoshikazu Yonemitsu, Masanori Miyazaki, Ri Ichiro Kohno, Yusuke Murakami, Toshinori Murata, Yoshinobu Goto, Toshiaki Tabata, Yasuji Ueda, Fumiko Ono, Toshimichi Suzuki, Naohide Ageyama, Keiji Terao, Mamoru Hasegawa, Katsuo Sueishi, Tatsuro Ishibashi

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


A phase 1 clinical trial evaluating the safety of gene therapy for patients with wet age-related macular degeneration (AMD) or retinoblastoma has been completed without problems. The efficacy of gene therapy for Leber's congenital amaurosis (LCA) was reported by three groups. Gene therapy may thus hold promise as a therapeutic method for the treatment of intractable ocular diseases. However, it will first be important to precisely evaluate the efficiency and safety of alternative gene transfer vectors in a preclinical study using large animals. In the present study, we evaluated the acute local (ophthalmic) and systemic toxicity of our simian immunodeficiency virus from African green monkeys (SIVagm)-based lentiviral vectors carrying human pigment epithelium-derived factor (SIV-hPEDF) for transferring genes into nonhuman primate retinas. Transient inflammation and elevation of intraocular pressure were observed in some animals, but these effects were not dose dependent. Electroretinograms (ERGs), including multifocal ERGs, revealed no remarkable change in retinal function. Histopathologically, SIV-hPEDF administration resulted in a certain degree of inflammatory reaction and no apparent structural destruction in retinal tissue. Regarding systemic toxicity, none of the animals died, and none showed any serious side effects during the experimental course. No vector leakage was detected in serum or urine samples. We thus propose that SIVagm-mediated stable gene transfer might be useful and safe for ocular gene transfer in a clinical setting.

Original languageEnglish
Pages (from-to)943-954
Number of pages12
JournalHuman Gene Therapy
Issue number9
Publication statusPublished - Sept 1 2009

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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