English to Chinese: Programmable protein delivery with a bacterial contractile injection system
General field: Science
Detailed field: Biology (-tech,-chem,micro-) | |
Source text - English
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 cells1–3, 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. | Translation - Chinese
内共生细菌已经进化出复杂的递送系统，使这些生物体能够与宿主的生物学特性相对接。其中一个例子是细胞外收缩注射系统（eCISs），它是一种类似注射器的大分子复合物，通过驱动其尖端穿过细胞膜，将蛋白质有效载荷注入真核细胞中。最近，eCISs被发现以小鼠细胞1-3为靶向，提高了这些系统应用于递送治疗用蛋白质的可能性。然而，eCISs是否能在人体细胞中发挥作用仍是未知数，且这些系统识别靶细胞的机制也不甚明了。我们在这篇文章中展示了，来自昆虫致病菌Photorhabdus asymbiotica的eCIS——Photorhabdus virulence cassette（PVC）的靶向选择是由PVC尾纤维的远端结合部位对目标受体的特异性识别所介导的。此外，在计算机模拟结构指导的尾纤维工程下，我们发现PVCs可以被重新编辑，以针对这些系统本身不靶向的生物体——包括人体细胞和小鼠，其效率接近100%。最后，我们发现，PVCs可以装载不同的蛋白质有效载荷，包括Cas9、碱基编辑器和毒素，并可以有效地将其送入人体细胞。我们的研究结果表明，PVC是一种可编程的蛋白质递送工具，可以应用于基因治疗、癌症治疗和生物控制等领域中。 |
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