Microsphere-liposome complexes protect adenoviral vectors from neutralising antibody without losses in transfection efficiency, in-vitro
Microsphere-liposome complexes protect adenoviral vectors from neutralising antibody without losses in transfection efficiency, in-vitro
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DOI：
10.1211/0022357044643
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发表时间：
2004-11-01
影响因子：
3.3
通讯作者：
Kalle, WHJ
中科院分区：
文献类型：
--
作者：
Steel, JC;Cavanagh, HMA;Kalle, WHJ
腺病毒载体已普遍用于基因治疗方案，但其使用的成功往往受到宿主对载体的免疫诱导的限制。暴露于腺病毒载体后，产生腺病毒特异性中和抗体，这限制了进一步给药。本研究检查了微球和脂质体的新型组合在体外环境中用于屏蔽腺病毒免受中和抗体的有效性。我们表明，脂质体是有效的保护腺病毒从中和抗体，这些复合物的微球的共轭增强保护水平。这项研究进一步揭示，先前中和的腺病毒仍然可以通过脂质体-细胞相互作用被转运到细胞中，并且仍然能够表达其基因，使得这种载体成为规避体液免疫应答的有效工具。我们还研究了使用复合物可能的副作用，即细胞毒性增加和转染效率降低。我们的结果表明，改变脂质体：腺病毒的比例可以降低载体的细胞毒性，以及增加转染效率。此外，在腺病毒感受态的细胞系中，用组合载体可实现与未复合的腺病毒载体相当的转染效率。
Adenoviral vectors have been commonly used in gene therapy protocols but the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced, which limits further administration. This study examines the effectiveness of a novel combination of microspheres and liposomes for the shielding of adenovirus from neutralising antibodies in an in-vitro setting. We show that liposomes are effective in the protection of adenovirus from neutralising antibody and that the conjugation of these complexes to microspheres augments the level of protection. This study further reveals that previously neutralised adenovirus may still be transported into the cell via liposome-cell interactions and is still capable of expressing its genes, making this vector an effective tool for circumvention of the humoral immune response. We also looked at possible side effects of using the complexes, namely increases in cytotoxicity and reductions in transfection efficiency. Our results showed that varying the liposome:adenovirus ratio can reduce the cytotoxicity of the vector as well as increase the transfection efficiency. In addition, in cell lines that are adenoviral competent, transfection efficiencies on par with uncomplexed adenoviral vectors were achievable with the combination vector.