Neutralizing antibody evasion ability of adenovirus vector induced by the bioconjugation of methoxypolyethylene glycol succinimidyl propionate (MPEG-SPA)
Neutralizing antibody evasion ability of adenovirus vector induced by the bioconjugation of methoxypolyethylene glycol succinimidyl propionate (MPEG-SPA)
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DOI：
10.1248/bpb.27.936
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发表时间：
2004-06-01
影响因子：
2
通讯作者：
Nakagawa, S
中科院分区：
文献类型：
--
作者：
Eto, Y;Gao, JQ;Nakagawa, S
腺病毒载体（adenovirus vectors，Ad）具有很高的转导效率，已广泛应用于动物模型的基因治疗，但临床应用非常有限。其主要原因之一是近80%的人体内存在抗Ad抗体。本研究尝试用琥珀酰亚胺丙酸酯活化的甲氧基聚乙二醇（MPEG）修饰Ad，并对PEG修饰Ad的中和抗体逃逸能力进行评价。结果表明，PEG-Ad对抗Ad中和抗体的保护能力比未修饰的Ad强。考虑到许多人携带抗Ad中和抗体，而Ad的再给药是治疗慢性疾病的必要条件，该策略也适用于其他载体，可用于开发改良载体。
Although adenovirus vectors (Ad) which possesses high transduction efficiency are widely used for gene therapy in animal models, clinical use is very limited. One of the main reason is that nearly 80% of human beings possess anti-Ad antibodies. In this study, we tried to modify Ad with methoxypolyethylene glycol (MPEG) activated by succinimidyl propionate, and, the neutralizing antibody evasion ability of PEGylated Ad was evaluated. The results demonstrated that PEG-Ad showed stronger protection ability against anti-Ad neutralizing antibody compared to that with unmodified-Ad. Considering there are many people carrying neutralizing antibody against Ad and readministration of Ad was necessary for treating chronic diseases, this strategy, which was also applicable to other vectors, can be used for developing improved vectors.