β-氨基酯聚合物有助于体内DNA转染和辅助质粒DNA免疫。
Beta-amino ester polymers facilitate in vivo DNA transfection and adjuvant plasmid DNA immunization.
作者信息
Greenland John R, Liu Huining, Berry David, Anderson Daniel G, Kim Woong-Ki, Irvine Darrell J, Langer Robert, Letvin Norman L
机构信息
Division of Viral Pathogenesis, Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113, 330 Brookline Avenue, Boston, MA 02215, USA.
出版信息
Mol Ther. 2005 Jul;12(1):164-70. doi: 10.1016/j.ymthe.2005.01.021.
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 (R2=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.
肌肉注射的质粒DNA在体内表达的增加对于基因治疗和质粒DNA疫苗接种的临床成功至关重要。我们从β-氨基酯文库中筛选聚合物，以其增强转基因表达的能力为指标，该能力通过β-半乳糖苷酶活性和细胞免疫反应来衡量。在该筛选中鉴定出的候选聚合物中，聚[(1,6-二(丙烯酰氧基乙氧基)己烷)-co-(4-氨基丁醇)]使质粒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，具有适度疏水主链和末端醇基的聚合物在体内最有效地促进转染。我们还观察到，在所有评估的聚合物-质粒DNA制剂中，峰值细胞免疫反应与转基因活性之间存在对数线性相关性(R2 = 0.93)，阐明了免疫原性与表达抗原量之间的关系。
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