Rod Outer Segment Development Influences AAV-Mediated Photoreceptor Transduction After Subretinal Injection

Human Gene Therapy
Lolita PetitClaudio Punzo

Abstract

Vectors based on the adeno-associated virus (AAV) are currently the preferred tools for delivering genes to photoreceptors (PR) in small and large animals. AAVs have been applied successfully in various models of PR dystrophies. However, unknown barriers still limit AAV's efficient application in several forms of severe PR degenerations due to insufficient transgene expression and/or treated cells at the time of injection. Optimizations of PR gene therapy strategies will likely benefit from the identification of the cellular factors that influence PR transduction. Interestingly, recent studies have shown that the AAV transduction profile of PRs differs significantly between neonatal and adult mouse retinas after subretinal injection. This phenomenon may provide clues to identify host factors that influence the efficiency of AAV-mediated PR transduction. This study demonstrates that rod outer segments are critical modulators of efficient AAV-mediated rod transduction. During retinal development, rod transduction correlated temporally and spatially with the differentiation order of PRs when vectors were introduced subretinally but not when introduced intravitreally. All subretinally injected vectors had an initial preference to t...Continue Reading

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Citations

Aug 23, 2017·Journal of Neural Engineering·Priya R Gupta, Rachel M Huckfeldt
Feb 26, 2019·International Journal of Retina and Vitreous·Parker E LudwigAdam C Janot
Feb 8, 2020·International Journal of Molecular Sciences·Marcela Garita-HernandezDeniz Dalkara
Feb 11, 2021·Pharmaceutics·Sanna KoponenSeppo Ylä-Herttuala
Aug 11, 2020·Molecular Therapy. Methods & Clinical Development·Scott H GreenwaldEric A Pierce
Sep 17, 2021·Investigative Ophthalmology & Visual Science·Xue-Jiao ChenZi-Bing Jin

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Methods Mentioned

BETA
GTPase
transfection
PCR
fluorescence microscopy

Software Mentioned

Photoshop
Imaris

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