May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Preclinical Long-Term Safety Study of Simian Immunodeficiency Virus (SIV)-Based Lentiviral Vector for Retinal Gene Transfer in Non-Human Primates
Author Affiliations & Notes
  • Y. Ikeda
    Kyushu University, Fukuoka-city, Japan
    Dept of Ophthalmology,
  • M. Miyazaki
    Kyushu University, Fukuoka-city, Japan
    Dept of Ophthalmology,
  • R.-I. Kohno
    Kyushu University, Fukuoka-city, Japan
    Dept of Ophthalmology,
  • Y. Murakami
    Kyushu University, Fukuoka-city, Japan
    Dept of Ophthalmology,
    Dept of Pathology,
  • Y. Yonemitsu
    Dept of Gene Therapy at the 21st Century COE program, Chiba University, Chiba-city, Japan
  • T. Murata
    Dept of Ophthalmology, Shinshu University, Matsumoto, Japan
  • Y. Goto
    Dept of Occupational Therapy, International University of Health and Welfare, Okawa, Japan
  • M. Hasegawa
    DNAVEC Corporation, Tsukuba, Japan
  • K. Sueishi
    Kyushu University, Fukuoka-city, Japan
    Dept of Pathology,
  • T. Ishibashi
    Kyushu University, Fukuoka-city, Japan
    Dept of Ophthalmology,
  • Footnotes
    Commercial Relationships  Y. Ikeda, None; M. Miyazaki, None; R. Kohno, None; Y. Murakami, None; Y. Yonemitsu, the Scientific Advisory Board of DNAVEC Corporation, C; T. Murata, None; Y. Goto, None; M. Hasegawa, COE, E; K. Sueishi, None; T. Ishibashi, None.
  • Footnotes
    Support  a Grant for the Promotion of Basic Science Research in Medical Frontiers from the Organization for Pharmaceutical Safety and Research (project No. MF-21)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5346. doi:https://doi.org/
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      Y. Ikeda, M. Miyazaki, R.-I. Kohno, Y. Murakami, Y. Yonemitsu, T. Murata, Y. Goto, M. Hasegawa, K. Sueishi, T. Ishibashi; Preclinical Long-Term Safety Study of Simian Immunodeficiency Virus (SIV)-Based Lentiviral Vector for Retinal Gene Transfer in Non-Human Primates. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5346. doi: https://doi.org/.

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

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Abstract

Purpose: : Recently, we have demonstrated the efficient and stable retinal gene transfer mediated by the non-pathogenic simian immunodeficiency virus (SIV)-based lentiviral vector as well as the therapeutic outcome in some animal models of retinal degeneration using recombinant SIV vectors carrying neurotrophic factors. Here, we report the long-term systemic and local effects following intraocular administration of SIV-hPEDF in Macaca fascicularis, as a preclinical safety study.

Methods: : Seven Macaca fascicularis were enrolled in this study. Approximately 20 µl of SIV-hPEDF (low titer: 2.5x107 transducing units [TU]/ml, n=4 and high titer: 2.5x108 TU/ml, n=3, respectively) were injected into subretinal space via a glass capillary tube. We undertook an ophthalmic examination, including slitlamp biomicroscopy, intraocular pressure (IOP) measurement, fundoscopic examination, fluorescein anigiography, and electroretinogram (ERG) measurement, and a systemic examination, including general body condition, vital sign, hematology, and blood and urine chemistry, during experimental course (2 years).

Results: : Long-lasting hPEDF expression was detected in the aqueous humor at the end of this study. No serious local effect was observed. Functional evaluation via ERGs including multi-focal ERGs revealed no remarkable change of the retinal functions. Neither dead animal nor serious side effect was found during experimental course.

Conclusions: : The current study indicated the long-term systemic and local safety of intraocular administration of SIV-hPEDF. This long-term safety study using large animals is encouraging for clinical application of retinal gene therapy for patients with retinitis pigmentosa.

Keywords: gene transfer/gene therapy • retinal degenerations: hereditary 
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