May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Systemic Examination of Simian Immunodeficiency Virus (SIV)–Based Lentivirus Vector for Retinal Gene Transfer in Non–Human Primates
Author Affiliations & Notes
  • R. Kono
    Dept Ophthal,
    Grad Sch Med Sci Kyushu Univ, Fukuoka–shi, Japan
  • Y. Ikeda
    Dept Ophthal,
    Grad Sch Med Sci Kyushu Univ, Fukuoka–shi, Japan
  • M. Miyazaki
    Dept Ophthal,
    Grad Sch Med Sci Kyushu Univ, Fukuoka–shi, Japan
  • Y. Yonemitsu
    Division of Pathophysiol and Exp Pathol, Dept Pathol,
    Grad Sch Med Sci Kyushu Univ, Fukuoka–shi, Japan
  • T. Murata
    Dept Ophthal, Shinshu University School of Med, Matsumoto–shi, Japan
  • N. Ageyama
    Tsukuba Primate Center, National Institute of Infectious Diseases, Tsukuba–shi, Japan
  • K. Terao
    Tsukuba Primate Center, National Institute of Infectious Diseases, Tsukuba–shi, Japan
  • M. Hasegawa
    DNAVEC Corporation, Tsukuba–shi, Japan
  • T. Ishibashi
    Dept Ophthal,
    Grad Sch Med Sci Kyushu Univ, Fukuoka–shi, Japan
  • K. Sueishi
    Division of Pathophysiol and Exp Pathol, Dept Pathol,
    Grad Sch Med Sci Kyushu Univ, Fukuoka–shi, Japan
  • Footnotes
    Commercial Relationships  R. Kono, None; Y. Ikeda, None; M. Miyazaki, None; Y. Yonemitsu, None; T. Murata, None; N. Ageyama, None; K. Terao, None; M. Hasegawa, DNAVEC Corporation E; T. Ishibashi, None; K. Sueishi, None.
  • Footnotes
    Support  Grant of Promotion of Basic Science Research for Pharmaceutical Safety and Research, Japan
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 5220. doi:
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      R. Kono, Y. Ikeda, M. Miyazaki, Y. Yonemitsu, T. Murata, N. Ageyama, K. Terao, M. Hasegawa, T. Ishibashi, K. Sueishi; Systemic Examination of Simian Immunodeficiency Virus (SIV)–Based Lentivirus Vector for Retinal Gene Transfer in Non–Human Primates . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5220.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Lentivirus vectors hold promise as a potential treatment modality for ocular diseases. However, the possible risks associated with the use of current human immunodeficiency virus (HIV)–based vectors slow their clinical application. We recently developed a novel lentivirus vector derived from the non–pathogenic simian immunodeficiency virus (SIVagm), to minimize these safety issues. Here, we report the acute systemic toxicity following intraocular administration of SIV–PEDF in Macaca fascicularis, as a preclinical safety study. Methods: Eleven Macaca fascicularis (body weight=2.35–5.63 kg) were enrolled in this study. Approximately 20 µl of SIV–PEDF (low titer: 2.5x107 transducing units [TU]/ml, equal to clinically used titer, high titer: 2.5x108 TU/ml, and max titer: 1.0x109 TU/ml, n=3, respectively) or control (balanced salt solution: BSS, n=2) were injected into subretinal space via a glass capillary tube. We undertook a systemic examination including general body condition, vital sign, hematology, and blood and urine chemistry during experimental course (3 months), and assessed the histology of general organ and the dissemination of vector genome by PCR assay. Results: SIV vector was efficiently transferred mainly to the retinal pigment epithelium and transgene expression was detected within 3 months. Neither dead animal nor serious side effect was found during experimental course. Transient increase of GOT and CPK was observed in all animals, suggesting a result of operation. Transient increase of serum IL–6 was found in some animals, but not dose–dependent. No vector genome was detected by PCR assay using the sample of whole blood and general organ. Conclusions: The current study exhibited the acute systemic safety of intraocular administration of SIV–PEDF (up to 40–times higher titer than clinically available titer). We are now conducting the long–term safety study to assess the possibility of carcinogenesis in non–human primates.

Keywords: gene transfer/gene therapy • retinal degenerations: cell biology • neuroprotection 
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