PEGylated cationic polylactides for hybrid biosynthetic gene delivery.
PEGylated cationic polylactides for hybrid biosynthetic gene delivery.
复制标题
用于杂化生物合成基因递送的阳离子阳离子多乳酸。
DOI：
10.1021/mp500683c
复制
发表时间：
2015-03-02
影响因子：
4.9
通讯作者：
Pfeifer, Blaine A.
中科院分区：
文献类型：
--
作者：
Jones, Charles H.;Chen, Chih-Kuang;Chen, Mingfu;Ravikrishnan, Anitha;Zhang, Hanguang;Gollakota, Akhila;Chung, Taichun;Cheng, Chong;Pfeifer, Blaine A.
基因疫苗接种的基本原理是，可以通过控制引入编码来自病原体的抗原蛋白的遗传物质以引发保护性免疫应答的形成来预防疾病。驱动这一过程的是载体的选择，该载体负责导航与基因递送相关的障碍。在这项工作中，我们扩大了一类新的杂交生物合成基因传递载体，由生物材料外涂层和细菌（大肠杆菌）的内核。具体而言，一系列新开发的可生物降解的阳离子聚乳酸（CPLA）和它们的聚乙二醇化变体被选择来研究低多分散指数（PDI）、电荷密度和聚乙二醇化对混合载体组装和基因递送功效的作用。组装后，杂交载体介导的增加的基因递送超过单独的细菌载体，包括具有增加的培养基蛋白质含量的测定，以突出由PEG官能化的CPLA组分提供的屏蔽性质。此外，经过广泛的表征聚合物的表面沉积，结果提示了一个新的模型，用于描述混合载体组装，包括细胞涂层和渗透的CPLA组件。总之，这些结果为下一代杂交生物合成基因递送载体的组装和应用提供了新的选择和见解。
Genetic vaccination is predicated on the underlying principle that diseases can be prevented by the controlled introduction of genetic material encoding antigenic proteins from pathogenic organisms to elicit the formation of protective immune responses. Driving this process is the choice of carrier that is responsible for navigating the obstacles associated with gene delivery. In this work, we expand upon a novel class of hybrid biosynthetic gene delivery vectors that are composed of a biomaterial outer coating and a bacterial (Escherichia coli) inner core. Specifically, a series of newly developed biodegradable cationic polylactides (CPLAs) and their PEGylated variants were selected to investigate the role of low polydispersity index (PDI), charge density, and PEGylation upon hybrid vector assembly and gene delivery efficacy. Upon assembly, hybrid vectors mediated increased gene delivery beyond that of the individual bacterial vector in isolation, including assays with increasing medium protein content to highlight shielding properties afforded by the PEG-functionalized CPLA component. Furthermore, after extensive characterization of surface deposition of the polymer, results prompted a new model for describing hybrid vector assembly that includes cellular coating and penetration of the CPLA component. In summary, these results provide new options and insight toward the assembly and application of next-generation hybrid biosynthetic gene delivery vectors.
登录
查看更多内容
影响因子：
4.9
作者：
Sunshine JC;Peng DY;Green JJ
通讯作者：
Green JJ
通过 Toll 样受体 4 介导的 IL-12 分泌，促进 1 型 T 辅助细胞对体内阳离子聚合物的反应。
影响因子：
14
作者：
Chen, Huan;Li, Pei;Zhang, Junfeng
通讯作者：
Zhang, Junfeng
影响因子：
14
作者：
Chen, Chih-Kuang;Jones, Charles H.;Cheng, Chong
通讯作者：
Cheng, Chong
DOI：
10.1073/pnas.1105777108
发表时间：
2011-08-23
影响因子：
11.1
作者：
Lee, Jaewoo;Sohn, Jang Wook;Sullenger, Bruce A.
通讯作者：
Sullenger, Bruce A.
影响因子：
3.7
作者：
Parsa, Saba;Wang, Yong;Pfeifer, Blaine A.
通讯作者：
Pfeifer, Blaine A.