Department of Urology, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi, Taiwan.
Department of Medical Research, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi, Taiwan.
Sci Rep. 2021 Jun 4;11(1):11889. doi: 10.1038/s41598-021-91328-7.
The ultimate goal of gene delivery vectors is to establish specific and effective treatments for human diseases. We previously demonstrated that human JC polyomavirus (JCPyV) virus-like particles (VLPs) can package and deliver exogenous DNA into susceptible cells for gene expression. For tissue-specific targeting in this study, JCPyV VLPs were conjugated with a specific peptide for bladder cancer (SPB) that specifically binds to bladder cancer cells. The suicide gene thymidine kinase was packaged and delivered by SPB-conjugated VLPs (VLP-SPBs). Expression of the suicide gene was detected only in human bladder cancer cells and not in lung cancer or neuroblastoma cells susceptible to JCPyV VLP infection in vitro and in vivo, demonstrating the target specificity of VLP-SPBs. The gene transduction efficiency of VLP-SPBs was approximately 100 times greater than that of VLPs without the conjugated peptide. JCPyV VLPs can be specifically guided to target particular cell types when tagged with a ligand molecule that binds to a cell surface marker, thereby improving gene therapy.
基因传递载体的最终目标是为人类疾病建立特定和有效的治疗方法。我们之前已经证明，人类 JC 多瘤病毒（JCPyV）病毒样颗粒（VLPs）可以将外源性 DNA 包装并递送至易感细胞中进行基因表达。在这项研究中，为了实现组织特异性靶向，我们将 JCPyV VLPs 与一种针对膀胱癌的特异性肽（SPB）缀合，该肽特异性结合膀胱癌细胞。自杀基因胸苷激酶由 SPB 缀合的 VLPs（VLP-SPBs）包装和递送。仅在体外和体内对 JCPyV VLP 感染敏感的人类膀胱癌细胞中检测到自杀基因的表达，而在肺癌或神经母细胞瘤细胞中未检测到，这表明 VLP-SPBs 的靶向特异性。VLP-SPBs 的基因转导效率比没有缀合肽的 VLPs 高约 100 倍。当 JCPyV VLPs 被标记与细胞表面标志物结合的配体分子时，可以被特异性引导至特定的靶细胞类型，从而改善基因治疗。
