Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-11

AUTHORS

T Kafri, U Blömer, D A Peterson, F H Gage, I M Verma

ABSTRACT

Successful gene therapy approaches will require efficient gene delivery and sustained expression of the transgene in recipients. A variety of methods, ranging from direct DNA delivery to infection with recombinant viruses containing foreign genes, have been developed, but they all have some major limitations that restrict their utility. We have described a human lentiviral (HIV)-based vector that can transduce non-dividing cells in vitro and deliver genes in vivo. With this vector, expression of transgenes in the brain has been detected for more than six months--the longest period tested so far. Because lentiviral vectors are pseudotyped with vesicular stomatitis virus G glycoprotein (VSVG; ref. 8), they can transduce a broad range of tissues and cell types. We now describe the ability of lentiviral vectors to introduce genes directly into liver and muscle. Sustained expression of green fluorescent protein (GFP), used as a surrogate for therapeutic protein, can be observed for more than 22 weeks in the liver. Similar long-term expression (more than eight weeks) was observed in transduced muscle. In contrast, little or no GFP could be detected in liver or muscle transduced with the Moloney murine leukaemia virus (M-MLV), a prototypic retroviral based vector. At a minimum, 3-4% of the total liver tissue was transduced by a single injection of 1-3 x 10(7) infectious units (I.U.) of recombinant HIV vector. Furthermore, no inflammation of recruitment of lymphocytes could be detected at the site of injection. Animals previously transduced with a lentiviral vector can be efficiently re-infected with lentiviral vectors. Additionally, we show that the requirement for lentiviral accessory proteins to establish efficient transduction in vivo is tissue dependent. More... »

PAGES

314-317

References to SciGraph publications

Journal

TITLE

Nature Genetics

ISSUE

3

VOLUME

17

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng1197-314

    DOI

    http://dx.doi.org/10.1038/ng1197-314

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1045816864

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9354796


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