Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2000-06

AUTHORS

Antonia Follenzi, Laurie E. Ailles, Silvia Bakovic, Massimo Geuna, Luigi Naldini

ABSTRACT

Gene-transfer vectors based on lentiviruses are distinguished by their ability to transduce non-dividing cells. The HIV-1 proteins Matrix, Vpr and Integrase have been implicated in the nuclear import of the viral genome in non-dividing cells. Here we show that a sequence within pol is also required in cis. It contains structural elements previously associated with the progress of reverse transcription in target cells. We restored these elements in cis within late-generation lentiviral vectors. The new vector transduced to a much higher efficiency several types of human primary cells, when both growing and growth-arrested, including haematopoietic stem cells assayed by long-term repopulation of NOD/SCID mice. On in vivo administration into SCID mice, the vector induced higher plasma levels of human clotting factor IX (F.IX) than non-modified vector. Our results indicate that nuclear translocation of the genome is a rate-limiting step in lentiviral infection of both dividing and non-dividing cells, and that it depends on protein and nucleic acid sequence determinants. Full rescue of this step in lentivirus-based vectors improves performance for gene-therapy applications. More... »

PAGES

ng0600_217

Journal

TITLE

Nature Genetics

ISSUE

2

VOLUME

25

Author Affiliations

From Grant

  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/76095

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    http://dx.doi.org/10.1038/76095

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10835641


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