Structure-Function Assessment of Mannosylated Poly(β-amino esters) upon Targeted Antigen Presenting Cell Gene Delivery.
Structure-Function Assessment of Mannosylated Poly(β-amino esters) upon Targeted Antigen Presenting Cell Gene Delivery.
复制标题
DOI：
10.1021/acs.biomac.5b00062
复制
发表时间：
2015-05-11
影响因子：
6.2
通讯作者：
Pfeifer, Blaine A.
中科院分区：
文献类型：
--
作者：
Jones, Charles H.;Chen, Mingfu;Gollakota, Akhila;Ravikrishnan, Anitha;Zhang, Guojian;Lin, Sharon;Tan, Myles;Cheng, Chong;Lin, Haiqing;Pfeifer, Blaine A.
抗原提呈细胞（APC）基因传递是一种很有前途的途径，可以调节免疫结果达到预期的状态。最近，我们的团队开发了一种递送方法来诱导apc介导的靶向和高水平的基因递送。在这些初步研究中，我们观察到基因传递过程中使用的载体与APC特异性结构-功能关系不同于目前的非APC细胞系，因此，强调需要重新评估APC基因转移背景下的载体相关参数。因此，我们描述了按分子量分层的第二代甘露糖基化聚（β-氨基酯）文库的合成和表征。为了更好地了解apc特异性调控聚合物基因传递的结构-功能关系，对文库进行了系统的表征(1)聚合物分子量，(2)相对甘露糖含量，(3)多聚体生物物理性质，(4)基因传递效果。在这个文库中，具有最低分子量和最高相对甘露糖含量的聚合物具有与商业对照相同或更好的基因传递转染效率。其中，最有效的聚合物在中等电荷密度（<10 mV）下形成最小的聚合物-质粒DNA复合物（~300 nm）。聚合物结构和多重生物物理性质的趋同表明了一种独特的作用模式，并为未来apc靶向聚合物的设计提供了一个框架。
Antigen presenting cell (APC) gene delivery is a promising avenue for modulating immunological outcomes toward a desired state. Recently, our group developed a delivery methodology to elicit targeted and elevated levels of APC-mediated gene delivery. During these initial studies, we observed APC-specific structure–function relationships with the vectors used during gene delivery that differ from current non-APC cell lines, thus, emphasizing a need to re-evaluate vector-associated parameters in the context of APC gene transfer. Thus, we describe the synthesis and characterization of a second-generation mannosylated poly(β-amino ester) library stratified by molecular weight. To better understand the APC-specific structure–function relationships governing polymeric gene delivery, the library was systematically characterized by (1) polymer molecular weight, (2) relative mannose content, (3) polyplex biophysical properties, and (4) gene delivery efficacy. In this library, polymers with the lowest molecular weight and highest relative mannose content possessed gene delivery transfection efficiencies as good as or better than commercial controls. Among this group, the most effective polymers formed the smallest polymer-plasmid DNA complexes (~300 nm) with moderate charge densities (<10 mV). This convergence in polymer structure and polyplex biophysical properties suggests a unique mode of action and provides a framework within which future APC-targeting polymers can be designed.
登录
查看更多内容
影响因子：
15
作者：
Bishop, Corey J.;Ketola, Tiia-Maaria;Tzeng, Stephany Y.;Sunshine, Joel C.;Urtti, Arto;Lemmetyinen, Helge;Vuorimaa-Laukkanen, Elina;Yliperttula, Marjo;Green, Jordan J.
通讯作者：
Green, Jordan J.
影响因子：
4.9
作者：
Sunshine JC;Peng DY;Green JJ
通讯作者：
Green JJ
影响因子：
17.1
作者：
Guerrero-Cazares, Hugo;Tzeng, Stephany Y.;Young, Noah P.;Abutaleb, Ameer O.;Quinones-Hinojosa, Alfredo;Green, Jordan J.
通讯作者：
Green, Jordan J.
影响因子：
16.1
作者：
Canine, Brenda F.;Hatefi, Arash
通讯作者：
Hatefi, Arash
影响因子：
14
作者：
Eltoukhy, Ahmed A.;Siegwart, Daniel J.;Alabi, Christopher A.;Rajan, Jay S.;Langer, Robert;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.