Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery.
Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery.
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DOI：
10.1016/j.biomaterials.2015.04.033
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发表时间：
2015-07
期刊：
影响因子：
14
通讯作者：
Pfeifer BA
中科院分区：
文献类型：
--
作者：
Jones CH;Gollakota A;Chen M;Chung TC;Ravikrishnan A;Zhang G;Pfeifer BA
鉴于抗生素耐药性微生物的兴起，基因疫苗接种是一种有前途的预防策略，可以快速设计和制造。促进这一过程的是载体的选择，这往往是具体情况和工程能力有限。此外，这些缺点通常与驱动载体介导的基因递送的结构-功能关系的不完全理解有关。在我们最初报告的混合细菌生物材料基因递送载体的基础上，使用一类甘露糖基化聚（β-氨基酯）完成了全面的结构-功能评估。通过自上而下的筛选方法，基于基因递送功效选择理想的聚合物，然后用于合成分层分子量聚合物文库。通过消除聚合物化学背景的贡献，我们能够完成作为（1）聚合物分子量，（2）相对甘露糖含量，（3）聚合物膜生物物理性质，（4）APC摄取特异性和（5）血清抑制的函数的基因递送的深入评估。总之，这项工作中的混合设计的灵活性和潜力突出了系统地探测载体相关特性的能力，用于开发翻译基因递送候选物。
Given the rise of antibiotic resistant microbes, genetic vaccination is a promising prophylactic strategy that enables rapid design and manufacture. Facilitating this process is the choice of vector, which is often situationally-specific and limited in engineering capacity. Furthermore, these shortcomings are usually tied to an incomplete understanding of the structure-function relationships driving vector-mediated gene delivery. Building upon our initial report of a hybrid bacterial-biomaterial gene delivery vector, a comprehensive structure-function assessment was completed using a class of mannosylated poly(beta-amino esters). Through a top-down screening methodology, an ideal polymer was selected on the basis of gene delivery efficacy and then used for the synthesis of a stratified molecular weight polymer library. By eliminating contributions of polymer chemical background, we were able to complete an in-depth assessment of gene delivery as a function of (1) polymer molecular weight, (2) relative mannose content, (3) polymer-membrane biophysical properties, (4) APC uptake specificity, and (5) serum inhibition. In summary, the flexibility and potential of the hybrid design featured in this work highlights the ability to systematically probe vector-associated properties for the development of translational gene delivery candidates.