Abstract
Transgenic expression of catalase in mitochondria using a transgenic strategy extends life span and prevents aging-related pathology in mice. However, transgenic overexpression is not suitable for a clinical application. Adeno-associated virus (AAV) is the most promising gene delivery vehicle. Here we outline strategies on the generation of an AAV vector expressing the mitochondria-targeted catalase gene (AV.RSV.MCAT). We also describe methods for evaluating physiological impact of AV.RSV.MCAT on muscle contractility and running performance in mice.
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References
Jackson MJ, O’Farrell S (1993) Free radicals and muscle damage. Br Med Bull 49:630–641
Tidball JG, Wehling-Henricks M (2007) The role of free radicals in the pathophysiology of muscular dystrophy. J Appl Physiol 102:1677–1686
Wei YH, Lee HC (2002) Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood) 227:671–682
Barja G, Herrero A (2000) Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals. FASEB J 14:312–318
Lee HC, Wei YH (2012) Mitochondria and aging. Adv Exp Med Biol 942:311–327
Bai J, Rodriguez AM, Melendez JA, Cederbaum AI (1999) Overexpression of catalase in cytosolic or mitochondrial compartment protects HepG2 cells against oxidative injury. J Biol Chem 274:26217–26224
Arita Y, Harkness SH, Kazzaz JA, Koo HC, Joseph A, Melendez JA, Davis JM, Chander A, Li Y (2006) Mitochondrial localization of catalase provides optimal protection from H2O2-induced cell death in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 290:L978–L986
Kohler JJ, Cucoranu I, Fields E, Green E, He S, Hoying A, Russ R, Abuin A, Johnson D, Hosseini SH, Raper CM, Lewis W (2009) Transgenic mitochondrial superoxide dismutase and mitochondrially targeted catalase prevent antiretroviral-induced oxidative stress and cardiomyopathy. Lab Invest 89:782–790
Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911
Treuting PM, Linford NJ, Knoblaugh SE, Emond MJ, Morton JF, Martin GM, Rabinovitch PS, Ladiges WC (2008) Reduction of age-associated pathology in old mice by overexpression of catalase in mitochondria. J Gerontol A Biol Sci Med Sci 63:813–822
Dai DF, Santana LF, Vermulst M, Tomazela DM, Emond MJ, MacCoss MJ, Gollahon K, Martin GM, Loeb LA, Ladiges WC, Rabinovitch PS (2009) Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation 119:2789–2797
Mao P, Manczak M, Calkins MJ, Truong Q, Reddy TP, Reddy AP, Shirendeb U, Lo HH, Rabinovitch PS, Reddy PH (2012) Mitochondria-targeted catalase reduces abnormal APP processing, amyloid beta production and BACE1 in a mouse model of Alzheimer’s disease: implications for neuroprotection and lifespan extension. Hum Mol Genet 21:2973–2990
Kay MA (2011) State-of-the-art gene-based therapies: the road ahead. Nat Rev Genet 12:316–328
Baoutina A, Alexander IE, Rasko JE, Emslie KR (2007) Potential use of gene transfer in athletic performance enhancement. Mol Ther 15:1751–1766
Mingozzi F, High KA (2011) Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Rev Genet 12:341–355
Buchlis G, Podsakoff GM, Radu A, Hawk SM, Flake AW, Mingozzi F, High KA (2012) Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer. Blood 119:3038–3041
Yue Y, Ghosh A, Long C, Bostick B, Smith BF, Kornegay JN, Duan D (2008) A single intravenous injection of adenoassociated virus serotype-9 leads to whole body skeletal muscle transduction in dogs. Mol Ther 16:1944–1952
Bostick B, Ghosh A, Yue Y, Long C, Duan D (2007) Systemic AAV-9 transduction in mice is influenced by animal age but not by the route of administration. Gene Ther 14:1605–1609
Liu M, Yue Y, Li D, Duan D (2007) Catalase overexpression does not impair extensor digitorum longus muscle function in normal mice. Muscle Nerve 36:833–841
Rex TS, Tsui I, Hahn P, Maguire AM, Duan D, Bennett J, Dunaief JL (2004) Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress. Hum Gene Ther 15:960–967
Qi X, Hauswirth WW, Guy J (2007) Dual gene therapy with extracellular superoxide dismutase and catalase attenuates experimental optic neuritis. Mol Vis 13:1–11
Guy J, Qi X, Hauswirth WW (1998) Adeno-associated viral-mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis. Proc Natl Acad Sci U S A 95:13847–13852
Li D, Lai Y, Yue Y, Rabinovitch PS, Hakim C, Duan D (2009) Ectopic catalase expression in mitochondria by adeno-associated virus enhances exercise performance in mice. PLoS One 4:e6673
McClure C, Cole KL, Wulff P, Klugmann M, Murray AJ (2011) Production and titering of recombinant adeno-associated viral vectors. J Vis Exp 27:e3348
Acknowledgments
The studies are supported by grants from the National Institutes of Health AR-49419 and the Muscular Dystrophy Association. We thank Dr. James Wilson (University of Pennsylvania, Philadelphia, PA) for providing the AAV-9 packaging plasmid.
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Li, D., Duan, D. (2013). Mitochondria-Targeted Antiaging Gene Therapy with Adeno-associated Viral Vectors. In: Tollefsbol, T. (eds) Biological Aging. Methods in Molecular Biology, vol 1048. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-556-9_13
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DOI: https://doi.org/10.1007/978-1-62703-556-9_13
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