Abstract:
:Lentiviral vectors are efficient gene delivery vehicles for therapeutic and research applications. In contrast to oncoretroviral vectors, they are able to infect most nonproliferating cells. In the liver, induction of cell proliferation dramatically improved hepatocyte transduction using all types of retroviral vectors. However, the precise relationship between hepatocyte division and transduction efficiency has not been determined yet. Here we compared gene transfer efficiency in the liver after in vivo injection of recombinant lentiviral or Moloney murine leukemia viral (MoMuLV) vectors in hepatectomized rats treated or not with retrorsine, an alkaloid that blocks hepatocyte division and induces megalocytosis. Partial hepatectomy alone resulted in a similar increase in hepatocyte transduction using either vector. In retrorsine-treated and partially hepatectomized rats, transduction with MoMuLV vectors dropped dramatically. In contrast, we observed that retrorsine treatment combined with partial hepatectomy increased lentiviral transduction to higher levels than hepatectomy alone. Analysis of nuclear ploidy in single cells showed that a high level of transduction was associated with polyploidization. In conclusion, endoreplication could be exploited to improve the efficiency of liver-directed lentiviral gene therapy.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Pichard V,Couton D,Desdouets C,Ferry Ndoi
10.1089/hum.2011.227subject
Has Abstractpub_date
2013-02-01 00:00:00pages
143-51issue
2eissn
1043-0342issn
1557-7422journal_volume
24pub_type
杂志文章abstract::Tumor angiogenesis is a rate-limiting factor for tumor growth, and the endothelial cells of tumor vessels display specific features that can be exploited for the selective delivery of cancer therapeutics. To specifically target exogenous genes to angiogenic tumor vessels, we generated a panel of vesicular stomatitis v...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403322168028
更新日期:2003-08-10 00:00:00
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journal_title:Human gene therapy
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journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:1995-07-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1089/hum.1996.7.12-1415
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pub_type: 杂志文章
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更新日期:2018-11-01 00:00:00
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pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/hum.1998.9.16-2407
更新日期:1998-11-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1992.3.1-11
更新日期:1992-02-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2014.109
更新日期:2015-03-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:1995-05-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Human gene therapy
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:2019-02-01 00:00:00