Induction of rapid and highly efficient expression of the human ND4 complex I subunit in the mouse visual system by self-complementary adeno-associated virus.

Archives of Ophthalmology
Rajeshwari D KoilkondaJohn Guy

Abstract

To demonstrate the high efficiency and rapidity of allotopic expression of a normal human ND4 subunit of complex I in the vertebrate retina using a self-complementary adeno-associated virus (scAAV) vector for ocular gene delivery to treat acute visual loss in Leber hereditary optic neuropathy (LHON). The nuclear-encoded human ND4 subunit fused to the P1 isoform of subunit C of adenosine triphosphate synthase (ATPc) mitochondrial targeting sequence and FLAG epitope was packaged in scAAV2 capsids or single-stranded (ss) AAV2 capsids. These constructs were injected into the vitreous cavities of mice. The contralateral eyes were injected with scAAV-green fluorescent protein (GFP). One week later, pattern electroretinograms and gene expression of the human ND4 subunit and GFP were evaluated. Quantitative analysis of ND4FLAG-injected eyes was assessed relative to Thy1.2-labeled retinal ganglion cells (RGCs). Pattern electroretinogram amplitudes remained normal in eyes inoculated with scAAV-ND4FLAG, ssAAV-ND4FLAG, and GFP. Confocal microscopy revealed the typical perinuclear mitochondrial expression of scAAV-ND4FLAG in almost the entire retinal flat mount. In contrast, scAAV-GFP expression was cytoplasmic and nuclear. Relative to Thy1...Continue Reading

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Citations

Jun 21, 2014·Visual Neuroscience·G Jane FarrarArpad Palfi
Jan 22, 2011·Journal of Ophthalmology·Rajeshwari D Koilkonda, John Guy
Feb 9, 2013·Science China. Life Sciences·Jacques ZaneveldRui Chen
Nov 2, 2016·Nucleic Acids Research·Amutha BoominathanMatthew S O'Connor
Nov 15, 2011·The Journal of Biological Chemistry·Claudio PunzoConstance L Cepko
Oct 7, 2017·Frontiers in Neuroscience·Killian S HanlonG Jane Farrar
Nov 8, 2020·Drugs·Giulia AmoreChiara La Morgia
Dec 4, 2020·The Application of Clinical Genetics·Srikanta Kumar PadhySubhadra Jalali
Dec 11, 2020·Science Translational Medicine·Patrick Yu-Wai-ManJosé-Alain Sahel
Nov 27, 2015·Ophthalmology·William J FeuerJohn Guy

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