如何将目的基因转运至特定的细胞器，并高效表达是癌症基因治疗的难题。本课题采用Fmoc多肽固相合成法及EDC反应制备了具有CD33靶向和细胞核定位双重功能的多肽纳米基因载体(aCD33-NLS-KALA-SA)，并设计利用该载体包载G3139构建aCD33-NLS-KALA-SA/G3139自组装纳米基因传递系统，用于急性骨髓性白血病的基因治疗。该传递系统通过自组装功能可以有效地包载和压缩G3139，通过载体中的抗体部分与肿瘤细胞表面的靶抗原特异性结合及KALA穿膜作用实现细胞内吞。通过载体α-螺旋构象转变可以逃离内涵体进入细胞质，通过NLS与核转运蛋白相互作用进入细胞核，从而增强基因的摄取和表达，最终实现对肿瘤细胞的核靶向及基因治疗。通过本课题开展，该传递系统可以克服G3139临床试验中转染率低的难点，提高G3139临床应用价值。为急性骨髓性白血病治疗带来新的前景。

How target gene would be transfected into specific organelle and expressed highly efficiently are challenging problems for cancer gene therapy. In this project, A new nano gene delivery vectors (aCD33-NLS-KALA-SA) was synthesized by Fmoc solid phase synthesis method and activation of EDC, the aim to overcome limitations, such as cell membrane and nuclear pores, offering attractive possibilities to enhance gene delivery. G3139 loaded aCD33-NLS-KALA-SA self-assembly nano gene delivery system for nucleus targeting were constructed to achieve acute myeloid leukemia (AML) gene therapy. This gene delivery system could encapsulate effectively G3139 by self-assembly, facilitate cellular internalization by antibody-antigen interaction and transmembrane ability of KALA, escape from endosomes by the transformation for α-helical conformation of vectors, rapidly position to the nucleus by proteins containing nuclear localization sequences and its recognization, enhance uptake and expression of gene, to achieve targeted delivery of genes into the nucleus and acute myeloid leukemia gene therapy. Through the studies in the project, This gene delivery system could overcome the difficulty of low transfection efficiency for G3139 in the clinical trials, improve the value of G3139 in clinical application. Also, the new therapeutic propect could be provided for acute myeloid leukemia.