尹志
(2023-03-31 00:12):
#paper https://doi.org/10.1038/s41586-023-05870-7. Nature, 2023, Programmable protein delivery with a
bacterial contractile injection system。这是今年张锋组的一篇新文章。文章介绍了一种叫做外胞质收缩注射系统(eCISs)的纳米机器,它们可以被重新编程以针对人类细胞并传递各种蛋白质负载,包括Cas9、碱基编辑器和毒素。这些系统可以用于基因治疗、癌症治疗和生物控制等领域。还讨论了利用收缩注射系统(CIS)作为蛋白质传递和基因编辑的潜在工具以及它们在生物技术和医学中的应用。基本都是实验,方法部分简直大开眼界,琳琅满目,基本看不懂;但看结论还是觉得挺有前瞻性的工作,而且使用了AF技术作为structure-guided engineering,这个很引起我的兴趣。总之,先浅浅仰慕读一下
Programmable protein delivery with a bacterial contractile injection system
翻译
Abstract:
Endosymbiotic bacteria have evolved intricate delivery systems that enable these organisms to interface with host biology. One example, the extracellular contractile injection systems (eCISs), are syringe-like macromolecular complexes that inject protein payloads into eukaryotic cells by driving a spike through the cellular membrane. Recently, eCISs have been found to target mouse cells, raising the possibility that these systems could be harnessed for therapeutic protein delivery. However, whether eCISs can function in human cells remains unknown, and the mechanism by which these systems recognize target cells is poorly understood. Here we show that target selection by the Photorhabdus virulence cassette (PVC)-an eCIS from the entomopathogenic bacterium Photorhabdus asymbiotica-is mediated by specific recognition of a target receptor by a distal binding element of the PVC tail fibre. Furthermore, using in silico structure-guided engineering of the tail fibre, we show that PVCs can be reprogrammed to target organisms not natively targeted by these systems-including human cells and mice-with efficiencies approaching 100%. Finally, we show that PVCs can load diverse protein payloads, including Cas9, base editors and toxins, and can functionally deliver them into human cells. Our results demonstrate that PVCs are programmable protein delivery devices with possible applications in gene therapy, cancer therapy and biocontrol.
翻译