β-amino ester polymers facilitate in vivo DNA transfection and adjuvant plasmid DNA immunization
β-amino ester polymers facilitate in vivo DNA transfection and adjuvant plasmid DNA immunization
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DOI：
10.1016/j.ymthe.2005.01.021
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发表时间：
2005-07-01
影响因子：
12.4
通讯作者：
Letvin, NL
中科院分区：
文献类型：
--
作者：
Greenland, JR;Liu, HN;Letvin, NL
肌内传递质粒DNA在体内表达的增加将是基因治疗和质粒DNA疫苗临床成功的关键。我们从β -半乳糖苷酶活性和细胞免疫反应测量的β -氨基酯库中筛选聚合物增强转基因表达的能力。在筛选到的候选物中，聚[（1,6-二（丙烯氧基乙氧基）己烷）-co-（4-氨基丁醇）]将质粒DNA转基因表达提高了7倍（P = 0.0001），其免疫原性提高了70% （P = 0.03）。我们发现具有适度疏水骨架和末端醇基的聚合物在体内最有效地促进了转染。我们还观察到，在所有评估的聚合质粒DNA配方中，细胞免疫应答峰值与转基因活性之间存在对数线性相关（R-2 = 0.93），阐明了免疫原性与表达抗原数量之间的关系。
Increased in vivo expression of intramuscularly delivered plasmid DNA will be essential for clinical success in gene therapy and plasmid DNA vaccination. We screened polymers from a library of beta-amino esters for their ability to augment transgene expression as measured by beta-galactosidase activity and cellular immune responses. Among the candidates identified in this screen, poly[(1,6-di(acryloxyethoxy)hexane)-co-(4-aminobutanol)] enhanced plasmid DNA transgene expression by sevenfold (P = 0.0001) and its immunogenicity by 70% (P = 0.03). We found that polymers with moderately hydrophobic backbones and terminal alcohol groups facilitated transfection most effectively in vivo. We also observed a log-linear correlation (R-2 = 0.93) between peak cellular immune responses and transgene activity in all evaluated polymer-plasmid DNA formulations, clarifying the relationship between immunogenicity and the quantity of expressed antigen.