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Gene transfer of Hodgkin cell lines via multivalent anti-CD30 scFv displaying bacteriophage.
BMC Molecular Biology Pub Date : 2008-04-16 , DOI: 10.1186/1471-2199-9-37
Yoon-Suk A Chung 1 , Katja Sabel , Martin Krönke , Alexander Klimka
Affiliation  

BACKGROUND The display of binding ligands, such as recombinant antibody fragments, on the surface of filamentous phage makes it possible to specifically attach these phage particles to target cells. After uptake of the phage, their internal single-stranded DNA is processed by the host cell, which allows transient expression of an encoded eukaryotic gene cassette. This opens the possibility to use bacteriophage as vectors for targeted gene therapy, although the transduction efficiency is very low. RESULTS Here we demonstrate the display of an anti-CD30 single chain variable fragment fused to the major coat protein pVIII on the surface of bacteriophage. These phage particles showed an improved binding and transduction efficiency of CD30 positive Hodgkin-lymphoma cells, compared to bacteriophage with the anti-CD30 single chain variable fragment fused to the minor coat protein pIII. CONCLUSION We can conclude from the results that the postulated multivalency of the anti-CD30-pVIII displaying bacteriophage combined with disseminated display of the anti-CD30 scFv on the whole particle surface is responsible for the improved gene transfer rate. These results mark an important step towards the use of phage particles as a cheap and safe gene transfer vehicle for the gene delivery of the desired target cells via their specific surface receptors.

中文翻译:

通过展示噬菌体的多价抗 CD30 scFv 对霍奇金细胞系进行基因转移。

背景技术在丝状噬菌体表面上展示结合配体,例如重组抗体片段,使得将这些噬菌体颗粒特异性地附着到靶细胞上成为可能。噬菌体被吸收后,它们的内部单链 DNA 被宿主细胞处理,从而允许编码的真核基因盒的瞬时表达。这开启了使用噬菌体作为靶向基因治疗载体的可能性,尽管转导效率非常低。结果在这里,我们展示了在噬菌体表面上展示了与主要外壳蛋白 pVIII 融合的抗 CD30 单链可变片段。这些噬菌体颗粒显示出改善的 CD30 阳性霍奇金淋巴瘤细胞的结合和转导效率,与具有与次要外壳蛋白 pIII 融合的抗 CD30 单链可变片段的噬菌体相比。结论我们可以从结果得出结论,抗-CD30-pVIII 展示噬菌体的假定多价结合抗-CD30 scFv 在整个颗粒表面的播散展示是提高基因转移率的原因。这些结果标志着朝着使用噬菌体颗粒作为廉价且安全的基因转移载体迈出了重要的一步,通过其特定的表面受体传递所需的靶细胞。结论我们可以从结果得出结论,抗-CD30-pVIII 展示噬菌体的假定多价结合抗-CD30 scFv 在整个颗粒表面的播散展示是提高基因转移率的原因。这些结果标志着朝着使用噬菌体颗粒作为廉价且安全的基因转移载体迈出了重要的一步,通过其特定的表面受体传递所需的靶细胞。结论我们可以从结果得出结论,抗-CD30-pVIII 展示噬菌体的假定多价结合抗-CD30 scFv 在整个颗粒表面的播散展示是提高基因转移率的原因。这些结果标志着朝着使用噬菌体颗粒作为廉价且安全的基因转移载体迈出了重要的一步,通过其特定的表面受体传递所需的靶细胞。
更新日期:2019-11-01
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