聚酰胺-胺型树枝状大分子及其衍生物在基因传递中的应用

Functionalized Polyamidoamine Dendrimer as Gene Delivery Vectors

基因治疗通过基因载体将治病基因导入病患的特异细胞以治疗心血管、神经系统疾病和癌症等。寻找安全高效的非病毒基因载体一直是基因治疗以及生物材料领域中的前沿课题。聚酰胺-胺型(PAMAM)树枝状高分子作为一类三维的、结构高度有序的新型载体,由于具有安全性好、易于修饰、携带外源基因容量大等特点,已经引起了广泛的关注。但是另一方面,合成步骤相对繁琐、后期产物纯化困难以及转染效率相对较低等问题限制了这类载体的进一步发展。本文结合本课题组的研究情况,针对如何提高PAMAM的转染效率以及增强其基因传递的靶向性等相关问题,对近几年在PAMAM树枝状分子修饰改性方面所做的一些有意义的工作进行了综述,并对前景进行了展望。

Gene therapy has emerged as the most promising therapeutic strategy for various human diseases such as cardiovascular disorders, neurological disease, and cancers by introducing functional gene into body via gene vectors. For the successful advancement of gene therapy, the further development of safer and more efficient gene delivery vectors has been an advanced topic in the researches of bioactive materials and gene delivery. Recently, polyamidoamine （PAMAM） dendrimers have been intensively studied because of their well-defined three-dimensional structures, relatively lower toxicity, possibility of facile modification, and capacity of carrying large gene segments. However, the applications of such molecules in gene delivery have been restricted by the complicated synthetic procedures and the laborious purification steps, as well as its lower transfection efficiency than virus. It is noted that surface modification of PAMAM dendrimers with series of bioactive molecules should intensively improve the transfection efficiency and biorecognition capacity. In this paper, an overview is presented with a focus on the PAMAM derivatives design and synthesis to enhance the gene delivery both in vitro and in vivo. We hope it may provide helpful insights for the further development of safe and efficient non-viral vectors.