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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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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.
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).
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.
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.
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