論文

査読有り
2016年4月

Malaria sporozoite protein expression enhances baculovirus-mediated gene transfer to hepatocytes

JOURNAL OF GENE MEDICINE
  • Takahiko Tamura
  • ,
  • Chiaki Kawabata
  • ,
  • Shunsuke Matsushita
  • ,
  • Miako Sakaguchi
  • ,
  • Shigeto Yoshida

担当区分
筆頭著者, 責任著者
18
4-6
開始ページ
75
終了ページ
85
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/jgm.2879
出版者・発行元
WILEY-BLACKWELL

BackgroundBaculovirus vector (BV) is able to transduce foreign genes into mammalian cells efficiently and safely by incorporating a mammalian promoter. In the present study, we tailored the surface proteins expressed by malaria sporozoites to enhance hepatocyte transduction. Sporozoites infect hepatocytes within minutes of initial entry into the blood circulation. Infectivity and hepatocyte-specific selectivity are mediated by the interplay between hepatocytes and sporozoite surface proteins. The circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein (TRAP) bind to the heparan sulfate proteoglycan on the hepatocyte surface and contribute to sporozoite infection and hepatocyte selectivity.
MethodsBVs displaying an ectodomain consisting of three different CSP variants (full-length, N-terminal and C-terminal) or TRAP on the virus envelope were constructed, and the resulting in vitro hepatocyte transduction efficiency was evaluated.
ResultsWe demonstrated improved hepatocyte transduction efficiency in BVs expressing CSP or TRAP ectodomains compared to BVs without malaria surface proteins. In addition, gene transduction efficiencies for BVs displaying CSP or TRAP are higher than those expressing the preS1 antigen of the hepatitis B virus.
ConclusionsBVs expressing CSP or TRAP in the ectodomain could represent a promising hepatocyte-specific gene delivery methodology. Copyright (c) 2016 John Wiley & Sons, Ltd.

Web of Science ® 被引用回数 : 2

リンク情報
DOI
https://doi.org/10.1002/jgm.2879
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27007512
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000378550800004&DestApp=WOS_CPL
共同研究・競争的資金等の研究課題
組織標的性を持つ遺伝子導入ベクターとしての次世代バキュロウイルスの開発

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