Bao Chun-Jie, Duan Jia-Lun, Xie Ying, Feng Xin-Ping, Cui Wei, Chen Song-Yue, Li Pei-Shan, Liu Yi-Xuan, Wang Jin-Ling, Wang Gui-Ling, Lu Wan-Liang
State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and Drug Delivery Systems, and School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
Nanomicro Lett. 2023 Aug 12;15(1):197. doi: 10.1007/s40820-023-01153-y.
Gene therapy offers potentially transformative strategies for major human diseases. However, one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue. Here, we report a novel virus-like nanoparticle, the bioorthgonal engineered virus-like recombinant biosome (reBiosome), for efficient gene therapies of cancer and inflammatory diseases. The mutant virus-like biosome (mBiosome) is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site, and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry. The results show that the reBiosome exhibits reduced virus-like immunogenicity, prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci (like tumor and arthritic tissue). Furthermore, reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems, respectively. In conclusion, this study develops a universal, safe and efficient platform for gene therapies for cancer and inflammatory diseases.
基因治疗为重大人类疾病提供了具有潜在变革性的策略。然而，基因治疗的关键挑战之一是开发一种能够将基因递送至特定组织的有效策略。在此，我们报告了一种新型病毒样纳米颗粒，即生物正交工程化病毒样重组生物小体（reBiosome），用于癌症和炎症性疾病的高效基因治疗。首先通过位点特异性密码子突变制备突变病毒样生物小体（mBiosome），以便在合理位点将4-叠氮基-L-苯丙氨酸展示在eBiosome的水疱性口炎病毒糖蛋白上，然后通过生物正交化学将弱酸响应性亲水性聚合物点击到mBiosome上制备reBiosome。结果表明，reBiosome表现出降低的病毒样免疫原性、延长的血液循环时间以及增强的向弱酸性病灶（如肿瘤和关节炎组织）的基因递送效率。此外，reBiosome通过分别递送基因编辑和沉默系统，在乳腺癌和关节炎中展现出强大的治疗效果。总之，本研究开发了一个用于癌症和炎症性疾病基因治疗的通用、安全且高效的平台。
