Therapeutic genome editing requires delivery of editing molecules to defined cell types, but targeting specificity and efficiency are currently limited. We hypothesized that properties inherent to immune cells, including tissue infiltration and programmed cell recognition, could be harnessed to engineer a cell-based delivery system. We show here that T cells can both produce and transfer editing machinery to target cells. In response to a programmable ligand, engineered T-lymphoid cells can transfer enzymes using complex spatiotemporal logic and deliver cargo in a cell contact-dependent or -independent manner. We demonstrate feasibility of this approach in primary human T cells, establishing a customizable genetic circuit for macromolecular delivery controlled by intercellular interactions.
1. 治疗性基因组编辑需要将编辑分子递送至特定细胞类型，但目前靶向特异性和效率有限。我们假设免疫细胞固有的特性（包括组织浸润和程序性细胞识别）可被利用来构建基于细胞的递送系统。本研究表明，T细胞既能产生编辑工具，也能将其转移至靶细胞。在可编程配体的刺激下，工程化T淋巴细胞能通过复杂的时空逻辑转移酶类，并以细胞接触依赖或非依赖的方式递送载荷。我们在原代人类T细胞中验证了该方法的可行性，建立了一种由细胞间相互作用调控的可定制大分子递送遗传回路。
Wasko, K. M. et al. · CC-BY 4.0