Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/32355
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dc.contributor.authorWesthaus, Adrian-
dc.contributor.authorCabanes Creus, Marti-
dc.contributor.authorDilworth, Kimberley L-
dc.contributor.authorZhu, Erhua-
dc.contributor.authorSalas, David-
dc.contributor.authorNavarro, Renina Gale-
dc.contributor.authorAmaya, Anais Karime-
dc.contributor.authorScott, Suzanne-
dc.contributor.authorKwiatek, Magdalena-
dc.contributor.authorMcCorkindale, Alexandra L-
dc.contributor.authorHayman, Tara E-
dc.contributor.authorFrahm, Silke-
dc.contributor.authorPerocheau, Dany-
dc.contributor.authorTran, Bang Manh-
dc.contributor.authorVincan, Elizabeth-
dc.contributor.authorWong, Sharon L-
dc.contributor.authorWaters, Shafagh A-
dc.contributor.authorRiddiough, Georgina E-
dc.contributor.authorPerini, Marcos V-
dc.contributor.authorWilson, Laurence O W-
dc.contributor.authorBaruteau, Julien-
dc.contributor.authorDiecke, Sebastian-
dc.contributor.authorGonzalez-Aseguinolaza, Gloria-
dc.contributor.authorSantilli, Giorgia-
dc.contributor.authorThrasher, Adrian J-
dc.contributor.authorAlexander, Ian Edward-
dc.contributor.authorLisowski, Leszek-
dc.date2023-
dc.date.accessioned2023-03-22T02:18:49Z-
dc.date.available2023-03-22T02:18:49Z-
dc.date.issued2023-03-16-
dc.identifier.citationHuman Gene Therapy 2023; 34(7-8)en_US
dc.identifier.issn1557-7422-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/32355-
dc.description.abstractThe liver is a prime target for in vivo gene therapies using recombinant adeno-associated viral vectors (rAAV). Multiple clinical trials have been undertaken for this target in the past 15 years, however we are still to see market approval of the first liver-targeted AAV-based gene therapy. Inefficient expression of the therapeutic transgene, vector-induced liver toxicity and capsid, and/or transgene-mediated immune responses reported at high vector doses are the main challenges to date. One of the contributing factors to the insufficient clinical outcomes, despite highly encouraging preclinical data, is the lack of robust, biologically- and clinically-predictive preclinical models. To this end, this study reports findings of a functional evaluation of six AAV vectors in twelve preclinical models of the human liver, with the aim to uncover which combination of models is the most relevant for the identification of AAV capsid variant for safe and efficient transgene delivery to primary human hepatocytes. The results, generated by studies in models ranging from immortalized cells, iPSC-derived and primary hepatocytes, and primary human hepatic organoids to in vivo models, increased our understanding of the strengths and weaknesses of each system. This should allow the development of novel gene therapies targeting the human liver.en_US
dc.language.isoeng-
dc.titleAssessment of pre-clinical liver models based on their ability to predict the liver-tropism of AAV vectors.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleHuman Gene Therapyen_US
dc.identifier.affiliationChildren's Medical Research Institute, 58454, Translational Vectorology, Westmead, New South Wales, Australia.en_US
dc.identifier.affiliationChildren's Medical Research Institute, 58454, Gene Therapy Research Unit, Westmead, New South Wales, Australia.en_US
dc.identifier.affiliationCentro de Investigacion Medica Aplicada, 90212, Pamplona, Spain.en_US
dc.identifier.affiliationChildren's Medical Research Institute, 58454, Translational Vectorology Group, 214 Hawkesbury Road, Westmead, New South Wales, Australia, 2145.en_US
dc.identifier.affiliationChildren's Medical Research Institute, 58454, Gene Therapy, Westmead, New South Wales, Australia.en_US
dc.identifier.affiliationChildren's Medical Research Institute, 58454, Translational Vectorology, Westmead, New South Wales, Australia.en_US
dc.identifier.affiliationThe Biological Threats Identification and Countermeasure Centre, Military Institute of Hygiene and Epidemiology, Pulawy, Poland.en_US
dc.identifier.affiliationInventia Life Science Pty Ltd, Sydney, New South Wales, Australia.en_US
dc.identifier.affiliationInventia Life Science Pty Ltd, Sydney, New South Wales, Australia.en_US
dc.identifier.affiliationMax Delbruck Centre for Molecular Medicine in the Helmholtz Association, 28341, Stem Cell Technology Platform, Berlin, Berlin, Germany.en_US
dc.identifier.affiliationUniversity College London, 4919, Genetics and Genomic Medicine, London, London, United Kingdom of Great Britain and Northern Ireland.en_US
dc.identifier.affiliationThe University of Melbourne, 2281, Molecular Oncology Group and Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia.en_US
dc.identifier.affiliationThe University of Melbourne, 2281, Molecular Oncology Group and Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia.en_US
dc.identifier.affiliationUniversity of New South Wales, 7800, Molecular and Integrative Cystic Fibrosis Research Centre, Sydney, New South Wales, Australia.en_US
dc.identifier.affiliationUniversity of New South Wales, 7800, Molecular and Integrative Cystic Fibrosis Research Centre, Sydney, New South Wales, Australia.en_US
dc.identifier.affiliationThe University of Melbourne, 2281, Department of Infectious Diseases, Melbourne Medical School, Melbourne, Victoria, Australia.en_US
dc.identifier.affiliationThe University of Melbourne, 2281, Department of Surgery, Austin Health Precinct, Melbourne, Victoria, Australia.en_US
dc.identifier.affiliationCommonwealth Scientific and Industrial Research Organisation, 2221, Australian e-Health Research Centre, Sydney, New South Wales, Australia.en_US
dc.identifier.affiliationUniversity College London, 4919, Genetics and Genomic Medicine Department, London, London, United Kingdom of Great Britain and Northern Ireland.en_US
dc.identifier.affiliationMax Delbruck Centre for Molecular Medicine in the Helmholtz Association, 28341, Stem Cell Technology Platform, Berlin, Berlin, Germany.en_US
dc.identifier.affiliationCenter for Applied Medical Research (CIMA)/Foundation for Applied Medical Research (FIMA) , Gene Therapy and Hepatology, Av. Pio XII, 55, Pamplona, Navarra, Spain, 31008.en_US
dc.identifier.affiliationUniversity College London, 4919, Institute of Child Health, London, London, United Kingdom of Great Britain and Northern Ireland.en_US
dc.identifier.affiliationUniversity College London, 4919, Institute of Child Health, London, London, United Kingdom of Great Britain and Northern Ireland.en_US
dc.identifier.affiliationSydney Children's Hospitals Network and Children's Medical Research Institute, Gene Therapy, Westmead, New South Wales, Australia.en_US
dc.identifier.affiliationChildren's Medical Research Institute, 58454, Translational Vectorology, Westmead, New South Wales, Australia.en_US
dc.identifier.affiliationSurgery (University of Melbourne)en_US
dc.identifier.doi10.1089/hum.2022.188en_US
dc.type.contentTexten_US
dc.identifier.pubmedid36927149-
local.name.researcherPerini, Marcos V
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.languageiso639-1en-
item.cerifentitytypePublications-
item.grantfulltextnone-
crisitem.author.deptSurgery (University of Melbourne)-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptHepatopancreatobiliary Surgery-
crisitem.author.deptSurgery (University of Melbourne)-
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