Efficient gene delivery into dendritic cells by fiber-mutant adenovirus vectors.

Efficient gene delivery into dendritic cells by fiber-mutant adenovirus vectors.
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通过纤维突变腺病毒载体将基因有效递送至树突状细胞。

DOI:
10.1006/bbrc.2001.4527
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发表时间:
2001
影响因子:
3.1
通讯作者:
T. Mayumi
T. Mayumi
中科院分区:
生物学4区
文献类型:
--
作者:
N. Okada;Y. Tsukada;S. Nakagawa;H. Mizuguchi;K. Mori;T. Saito;T. Fujita;A. Yamamoto;T. Hayakawa;T. Mayumi

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最近的研究表明,腺病毒载体(Ad)转基因的树突状细胞(DC)在免疫治疗中是有用的,而高剂量的Ad需要足够的基因转导到DC中。RT-PCR分析表明,DC对Ad介导的基因转移的相对抵抗是由于缺乏柯萨奇-腺病毒受体的表达,并且DC表达了足够的α(V)-整合素。因此,我们研究了在纤维结节中含有Arg-Gly-Asp(RGD)序列的纤维突变体Ad能否有效地将LacZ基因转导和表达到DC中。无论是在小鼠树突状细胞系还是在正常人树突状细胞(NHDC)上,纤维突变体Ad的基因传递效率均高于常规Ad。此外,在8000个载体颗粒/细胞条件下,纤维突变体Ad转导NHDC的β-半乳糖苷酶活性是普通Ad的70倍。我们认为,α(V)-整合素靶向的Ad是一种非常强大的工具,可以用来实施基于DC的疫苗接种策略。
Recent studies have demonstrated the usefulness of dendritic cells (DCs) genetically modified by adenovirus vectors (Ad) to immunotherapy, while sufficient gene transduction into DCs is required for high doses of Ad. The RT-PCR analysis revealed that the relative resistance of DCs to Ad-mediated gene transfer is due to the absence of Coxsackie-adenovirus receptor expression, and that DCs expressed adequate alpha(v)-integrins. Therefore, we investigated whether fiber-mutant Ad containing the Arg-Gly-Asp (RGD) sequence in the fiber knob can efficiently transduce and express high levels of the LacZ gene into DCs. The gene delivery by fiber-mutant Ad was more efficient than that by conventional Ad in both murine DC lines and normal human DCs (NHDC). Furthermore, NHDC transduced with fiber-mutant Ad and conventional Ad at 8000-vector particles/cell resulted in a 70-fold difference in beta-galactosidase activity. We propose that alpha(v)-integrin-targeted Ad is a very powerful tool with which to implement DC-based vaccination strategies.
DOI: 10.1089/hum.1998.9.17-2577
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