In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions View Full Text


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Article Info

DATE

2022-08-25

AUTHORS

Clara T. Nicolas, Caitlin J. VanLith, Raymond D. Hickey, Zeji Du, Lori G. Hillin, Rebekah M. Guthman, William J. Cao, Benjamin Haugo, Annika Lillegard, Diya Roy, Aditya Bhagwate, Daniel O’Brien, Jean-Pierre Kocher, Robert A. Kaiser, Stephen J. Russell, Joseph B. Lillegard

ABSTRACT

Conventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)−1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression to liver fibrosis, liver failure, and activation of tumorigenic pathways. Here we demonstrate cure of HT1 by direct, in vivo administration of a therapeutic lentiviral vector targeting the expression of a human fumarylacetoacetate hydrolase (FAH) transgene in the porcine model of HT1. This therapy is well tolerated and provides stable long-term expression of FAH in pigs with HT1. Genomic integration displays a benign profile, with subsequent fibrosis and tumorigenicity gene expression patterns similar to wild-type animals as compared to NTBC-treated or diseased untreated animals. Indeed, the phenotypic and genomic data following in vivo lentiviral vector administration demonstrate comparative superiority over other therapies including ex vivo cell therapy and therefore support clinical application of this approach. More... »

PAGES

5012

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-022-32576-7

    DOI

    http://dx.doi.org/10.1038/s41467-022-32576-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1150490871

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/36008405


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    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41467-022-32576-7'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41467-022-32576-7'


     

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