Sökning: WFRF:(Larbi A) > (2015-2019) > A novel adeno-assoc...
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000 | 06024naa a2200733 4500 | |
001 | oai:lup.lub.lu.se:2bac8ee7-ab26-4a25-8f23-533ebd554c17 | |
003 | SwePub | |
008 | 180917s2018 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/2bac8ee7-ab26-4a25-8f23-533ebd554c172 URI |
024 | 7 | a https://doi.org/10.1093/brain/awy1262 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Tordo, Julieu King's College London4 aut |
245 | 1 0 | a A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency |
264 | c 2018-05-16 | |
264 | 1 | b Oxford University Press (OUP),c 2018 |
300 | a 18 s. | |
520 | a Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng |
653 | a adeno-associated virus | |
653 | a capsid engineering | |
653 | a lysosomal transmembrane enzyme | |
653 | a mucopolysaccharidosis | |
653 | a neurotropism | |
700 | 1 | a O'Leary, Claireu University of Manchester4 aut |
700 | 1 | a Antunes, André S.L.M.u King's College London4 aut |
700 | 1 | a Palomar, Nuriau King's College London4 aut |
700 | 1 | a Aldrin-Kirk, Patricku Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups4 aut0 (Swepub:lu)med-pca |
700 | 1 | a Basche, Marku University College London4 aut |
700 | 1 | a Bennett, Antonetteu Florida Museum Natural History4 aut |
700 | 1 | a D'Souza, Zelphau University of Manchester4 aut |
700 | 1 | a Gleitz, Hélèneu University of Manchester4 aut |
700 | 1 | a Godwin, Annieu University of Manchester4 aut |
700 | 1 | a Holley, Rebecca J.u University of Manchester4 aut |
700 | 1 | a Parker, Helenu University of Manchester4 aut |
700 | 1 | a Liao, Ai Yinu University of Manchester4 aut |
700 | 1 | a Rouse, Paulu University of Manchester4 aut |
700 | 1 | a Youshani, Amir Saamu University of Manchester4 aut |
700 | 1 | a Dridi, Larbiu Centre Hospitalier Universitaire Sainte-Justine4 aut |
700 | 1 | a Martins, Carlau Centre Hospitalier Universitaire Sainte-Justine4 aut |
700 | 1 | a Levade, Thierryu Toulouse University Hospital4 aut |
700 | 1 | a Stacey, Kevin B.u University of Manchester4 aut |
700 | 1 | a Davis, Daniel M.u University of Manchester4 aut |
700 | 1 | a Dyer, Adamu King's College London4 aut |
700 | 1 | a Clément, Nathalieu Florida Museum Natural History4 aut |
700 | 1 | a Björklund, Tomasu Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups4 aut0 (Swepub:lu)mphy-tbj |
700 | 1 | a Ali, Robin R.u University College London4 aut |
700 | 1 | a Agbandje-McKenna, Mavisu Florida Museum Natural History4 aut |
700 | 1 | a Rahim, Ahad A.u University College London4 aut |
700 | 1 | a Pshezhetsky, Alexeyu Centre Hospitalier Universitaire Sainte-Justine4 aut |
700 | 1 | a Waddington, Simon N.u University College London,University of the Witwatersrand4 aut |
700 | 1 | a Linden, R. Michaelu King's College London4 aut |
700 | 1 | a Bigger, Brian W.u University of Manchester4 aut |
700 | 1 | a Henckaerts, Elsu King's College London4 aut |
710 | 2 | a King's College Londonb University of Manchester4 org |
773 | 0 | t Braind : Oxford University Press (OUP)g 141:7, s. 2014-2031q 141:7<2014-2031x 0006-8950x 1460-2156 |
856 | 4 | u http://dx.doi.org/10.1093/brain/awy126x freey FULLTEXT |
856 | 4 | u https://academic.oup.com/brain/article-pdf/141/7/2014/25137174/awy126.pdf |
856 | 4 8 | u https://lup.lub.lu.se/record/2bac8ee7-ab26-4a25-8f23-533ebd554c17 |
856 | 4 8 | u https://doi.org/10.1093/brain/awy126 |
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