Gene therapy promises to treat diseases that arise from genetic abnormalities by correcting the underlying cause of the disease rather than treating the associated symptoms. Successful transfer of nucleic acids into cells requires efficient delivery vehicles that protect the cargo and can penetrate the appropriate cellular barriers before releasing their contents. Many viral vectors and synthetic polycationic vectors for nucleic acid delivery do not translate well from in vitro to in vivo applications due to their instability and toxicity. We synthesized and characterized a library of biocompatible low charge density polymers from a family of poly(amine-co-ester) (PACE) terpolymers produced via enzyme catalyzed polymerization. PACE polymers are highly customizable; we found that the terpolymer composition can be optimized to produce efficient transfection of various nucleic acids—including DNA plasmids, mRNA, and siRNA—in specific cell types with low toxicity. Our findings suggest that the unique tunability of PACEs offers new tools for gene therapy and other biomedical applications.

中文翻译：

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用于定制核酸输送和其他生物医学应用的可生物降解聚（胺-酯）聚合物的可调性

基因疗法有望通过纠正疾病的根本原因而不是治疗相关症状来治疗由遗传异常引起的疾病。将核酸成功转移到细胞中需要有效的递送载体来保护货物并能够在释放其内容物之前穿透适当的细胞屏障。许多用于核酸递送的病毒载体和合成聚阳离子载体由于其不稳定性和毒性而不能很好地从体外应用到体内应用。我们从通过酶催化聚合生产的聚（胺共酯）（PACE）三元共聚物家族中合成并表征了生物相容性低电荷密度聚合物库。PACE 聚合物具有高度可定制性；我们发现，可以对三元共聚物组合物进行优化，以在特定细胞类型中高效转染各种核酸（包括 DNA 质粒、mRNA 和 siRNA），且毒性较低。我们的研究结果表明，PACE 独特的可调性为基因治疗和其他生物医学应用提供了新工具。