Efficient lentiviral transduction of liver requires cell cycling in vivo

Frank Park, Kazuo Ohashi, Winnie Chiu, Luigi Naldini, Kay Mark A

Research output: Contribution to journalArticle

195 Citations (Scopus)

Abstract

Human-immunodeficiency-virus (HIV)-based lentiviral vectors are a promising tool for in vivo gene therapy. Unlike Moloney-murine-leukaemia- based retroviruses (MLV), lentiviruses are believed to stably transduce quiescent (non-cycling) cells in various organs. No previous studies, however, have directly established the cell-cycle status of any transduced cell type at the time of vector administration in vivo. In vitro studies using wild-type HIV or HIV-based vectors have shown that, in some cases, cell-cycle activation is required for infection, even though cellular mitosis is not an absolute requirement for integration. Even if the block in reverse transcription is overcome in quiescent T cells, productive infection by HIV cannot be rescued in the absence of cell-cycle activation. The potential use of these vectors for gene therapy prompted our study, which establishes a cell-cycle requirement for efficient transduction of hepatocytes in vivo.

Original languageEnglish
Pages (from-to)49-52
Number of pages4
JournalNature Genetics
Volume24
Issue number1
DOIs
Publication statusPublished - 2000

Fingerprint

Cell Cycle
HIV
Liver
Genetic Therapy
Lentivirus
Retroviridae
Infection
Mitosis
Reverse Transcription
Hepatocytes
Leukemia
T-Lymphocytes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Efficient lentiviral transduction of liver requires cell cycling in vivo. / Park, Frank; Ohashi, Kazuo; Chiu, Winnie; Naldini, Luigi; Mark A, Kay.

In: Nature Genetics, Vol. 24, No. 1, 2000, p. 49-52.

Research output: Contribution to journalArticle

Park, Frank ; Ohashi, Kazuo ; Chiu, Winnie ; Naldini, Luigi ; Mark A, Kay. / Efficient lentiviral transduction of liver requires cell cycling in vivo. In: Nature Genetics. 2000 ; Vol. 24, No. 1. pp. 49-52.
@article{f38c2d9d5e174806bd7e3d0632b29f27,
title = "Efficient lentiviral transduction of liver requires cell cycling in vivo",
abstract = "Human-immunodeficiency-virus (HIV)-based lentiviral vectors are a promising tool for in vivo gene therapy. Unlike Moloney-murine-leukaemia- based retroviruses (MLV), lentiviruses are believed to stably transduce quiescent (non-cycling) cells in various organs. No previous studies, however, have directly established the cell-cycle status of any transduced cell type at the time of vector administration in vivo. In vitro studies using wild-type HIV or HIV-based vectors have shown that, in some cases, cell-cycle activation is required for infection, even though cellular mitosis is not an absolute requirement for integration. Even if the block in reverse transcription is overcome in quiescent T cells, productive infection by HIV cannot be rescued in the absence of cell-cycle activation. The potential use of these vectors for gene therapy prompted our study, which establishes a cell-cycle requirement for efficient transduction of hepatocytes in vivo.",
author = "Frank Park and Kazuo Ohashi and Winnie Chiu and Luigi Naldini and {Mark A}, Kay",
year = "2000",
doi = "10.1038/71673",
language = "English",
volume = "24",
pages = "49--52",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Efficient lentiviral transduction of liver requires cell cycling in vivo

AU - Park, Frank

AU - Ohashi, Kazuo

AU - Chiu, Winnie

AU - Naldini, Luigi

AU - Mark A, Kay

PY - 2000

Y1 - 2000

N2 - Human-immunodeficiency-virus (HIV)-based lentiviral vectors are a promising tool for in vivo gene therapy. Unlike Moloney-murine-leukaemia- based retroviruses (MLV), lentiviruses are believed to stably transduce quiescent (non-cycling) cells in various organs. No previous studies, however, have directly established the cell-cycle status of any transduced cell type at the time of vector administration in vivo. In vitro studies using wild-type HIV or HIV-based vectors have shown that, in some cases, cell-cycle activation is required for infection, even though cellular mitosis is not an absolute requirement for integration. Even if the block in reverse transcription is overcome in quiescent T cells, productive infection by HIV cannot be rescued in the absence of cell-cycle activation. The potential use of these vectors for gene therapy prompted our study, which establishes a cell-cycle requirement for efficient transduction of hepatocytes in vivo.

AB - Human-immunodeficiency-virus (HIV)-based lentiviral vectors are a promising tool for in vivo gene therapy. Unlike Moloney-murine-leukaemia- based retroviruses (MLV), lentiviruses are believed to stably transduce quiescent (non-cycling) cells in various organs. No previous studies, however, have directly established the cell-cycle status of any transduced cell type at the time of vector administration in vivo. In vitro studies using wild-type HIV or HIV-based vectors have shown that, in some cases, cell-cycle activation is required for infection, even though cellular mitosis is not an absolute requirement for integration. Even if the block in reverse transcription is overcome in quiescent T cells, productive infection by HIV cannot be rescued in the absence of cell-cycle activation. The potential use of these vectors for gene therapy prompted our study, which establishes a cell-cycle requirement for efficient transduction of hepatocytes in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0033986340&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033986340&partnerID=8YFLogxK

U2 - 10.1038/71673

DO - 10.1038/71673

M3 - Article

VL - 24

SP - 49

EP - 52

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 1

ER -