Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiency.

Autor:	Zhang H; Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 925 N 87 Street, Milwaukee, WI 53226, USA., Sajdak BS; Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 925 N 87 Street, Milwaukee, WI 53226, USA.; Morgridge Institute for Research, Madison, WI 53715, USA., Merriman DK; Department of Biology, University of Wisconsin Oshkosh, Oshkosh, WI 54901, USA., Carroll J; Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 925 N 87 Street, Milwaukee, WI 53226, USA., Lipinski DM; Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 925 N 87 Street, Milwaukee, WI 53226, USA.; Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford OX1 2JD, UK.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2021 Jun 12; Vol. 22, pp. 96-106. Date of Electronic Publication: 2021 Jun 12 (Print Publication: 2021).
DOI:	10.1016/j.omtm.2021.06.005
Abstrakt:	Intravitreal injection is the most widely used injection technique for ocular gene delivery. However, vector diffusion is attenuated by physical barriers and neutralizing antibodies in the vitreous. The 13-lined ground squirrel (13-LGS), as in humans, has a larger relative vitreous body volume than the more common rodent models such as rats and mice, which would further reduce transduction efficiency with the intravitreal injection route. We report here a "pre-retinal" injection approach that leads to detachment of the posterior hyaloid membrane and delivers vector into the space between vitreous and inner retina. Vectors carrying a ubiquitously expressing mCherry reporter were injected into the deep vitreous or pre-retinal space in adult wild-type 13-LGSs. Then, adeno-associated virus (AAV)-mediated mCherry expression was evaluated with non-invasive imaging, immunofluorescence, and flow cytometry. Compared to deep vitreous delivery, pre-retinal administration achieved pan-retinal gene expression with a lower vector dose volume and significantly increased the number of transduced cone photoreceptors. These results suggest that pre-retinal injection is a promising tool in the development of gene therapy strategies in animal models and is a potential approach for use in human research, particularly in younger individuals with an intact posterior hyaloid membrane and stable vitreous. Competing Interests: The authors declare no competing interests. (© 2021 The Author(s).)
Databáze:	MEDLINE
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