Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines
Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines
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DOI：
10.1038/nmat1075
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发表时间：
2004-03-01
期刊：
影响因子：
41.2
通讯作者：
Putnam, D
中科院分区：
文献类型：
--
作者：
Wang, C;Ge, Q;Putnam, D
使用质粒DNA的基因疫苗接种为实现有效的免疫应答提供了独特的机会，而没有许多常规疫苗的潜在限制。在这里，我们报告的合成生物可降解聚合物的设计，特别是提高DNA疫苗在体内的功效。我们用分子工程技术聚（原酸酯）微球对细胞无毒，保护DNA免于降解，能够被抗原呈递细胞摄取，并响应于吞噬体pH快速释放DNA。（原酸酯），其与适应性免疫的自然发展同步释放DNA疫苗，在小鼠中引发不同的原发性和继发性体液和细胞免疫应答，并抑制携带模型抗原的肿瘤细胞的生长。随着进一步的研究，这种聚合物微粒系统可能对推进DNA疫苗的临床应用以及其他基于核酸的治疗病毒感染和癌症具有意义。
Genetic vaccination using plasmid DNA presents a unique opportunity for achieving potent immune responses without the potential limitations of many conventional vaccines. Here we report the design of synthetic biodegradable polymers specifically for enhancing DNA vaccine efficacy in vivo. We molecularly engineered poly(ortho ester) microspheres that are non-toxic to cells, protect DNA from degradation, enable uptake by antigen-presenting cells, and release DNA rapidly in response to phagosomal pH. One type of microsphere of poly(ortho esters) that releases DNA vaccines in synchrony with the natural development of adaptive immunity, elicited distinct primary and secondary humoral and cellular immune responses in mice, and suppressed the growth of tumour cells bearing a model antigen. This polymer microparticulate system could, with further study, have implications for advancing the clinical utility of DNA vaccines as well as other nucleic-acid-based therapeutics against viral infections and cancer.