CATIONIC POLYMER OF NETWORK STRUCTURE FOR PACKING NUCLEIC ACIDS INTRA-MOLECULARLY
    4.
    发明申请
    CATIONIC POLYMER OF NETWORK STRUCTURE FOR PACKING NUCLEIC ACIDS INTRA-MOLECULARLY 审中-公开
    分子内包裹核酸的网络结构阳离子聚合物

    公开(公告)号:WO2018053795A1

    公开(公告)日:2018-03-29

    申请号:PCT/CN2016/099849

    申请日:2016-09-23

    发明人: JIN, Tuo CHEN, Shun

    摘要: This invention demonstrated a unique cationic polymer that possesses a number features essential for systemic delivery of nucleic acids simultaneously. First, this polymer was synthesized by Zeta potential-regulated condensation of linear and branched amino group bearing oligomers through imidazole-4, 5-imine linkages, wherein the polymer diameter can be precisely adjusted from tens to hundreds nanometers by Zeta potential determinates such NaCl concentration. Most interestingly, the polymer was structured with sufficient network cavity to pack plenty copies of siRNA intramolecularly to form a polyplex of single polymer molecule. In addition, the polymer backbone degraded readily to non-toxic species and released nucleic acids in response to cellular environment due to the pKa (5.9) of its aromatically conjugated imine linage. Finally, the polyplex of single polymer molecule can be further encapsulated by a self-assembled a unilamella membrane of rationally designed triblock copolymer to which selected functional components such as cell targeting agents can be immobilized in optimized population. The lack of medicinally feasible synthetic carriers remains as the standing-hurdle blocking nucleic acids to covert from therapeutic actives to practical medicines. The present invention may serve as a "universal" vehicle to equip with variety of delivery functions for its defined structure and compatible flexibility.

    摘要翻译: 本发明展示了一种独特的阳离子聚合物,其具有对于同时全身递送核酸必不可少的数个特征。 首先,该聚合物通过咪唑-4,5-亚胺键的直链和支链氨基基团低聚物的Zeta电位调节缩合合成,其中聚合物直径可以通过Zeta电位确定如NaCl浓度从数十至数百纳米精确调节 。 最有趣的是,聚合物结构具有足够的网络空腔以分子内包装大量siRNA以形成单聚合物分子的多聚体。 另外,由于其芳香族共轭亚胺谱系的pKa(5.9),聚合物骨架容易降解成无毒物质并释放核酸以响应细胞环境。 最后,单聚合物分子的多聚体可以通过自组装的合理设计的三嵌段共聚物的单层膜进一步包封,选择的功能组分如细胞靶向剂可以固定在优化的群体中。 医学上可行的合成载体的缺乏仍然是阻止核酸从治疗活性成分转化为实际药物的常规障碍。 本发明可以用作“通用” 车辆配置各种交付功能的定义结构和兼容的灵活性。