Zhang Xiaowei, Mille-Fragoso Luis S, Eerik Kaseniit K, Lee Arden P, Zhang Meng, Call Connor C, Hu Yixin, Xie Yunxin, Gao Xiaojing J
Department of Bioengineering, Stanford University; Stanford, 94305, USA.
Sarafan ChEM-H, Stanford University; Stanford, 94305, USA.
bioRxiv. 2024 Nov 24:2024.05.03.592453. doi: 10.1101/2024.05.03.592453.
Inspired by the power of transcriptional synthetic receptors and hoping to complement them to expand the toolbox for cell engineering, we establish LIDAR (Ligand-Induced Dimerization Activating RNA editing), a modular post-transcriptional synthetic receptor platform that harnesses RNA editing by ADAR. LIDAR is compatible with various receptor architectures in different cellular contexts, and enables the sensing of diverse ligands and the production of functional outputs. Furthermore, LIDAR can sense orthogonal signals in the same cell and produce synthetic spatial patterns, potentially enabling the programming of complex multicellular behaviors. Finally, LIDAR is compatible with compact encoding and can be delivered as synthetic mRNA. Thus, LIDAR expands the family of synthetic receptors, holding the promise to empower basic research and therapeutic applications.
受转录合成受体强大功能的启发,并希望对其进行补充以扩展细胞工程的工具库,我们建立了LIDAR(配体诱导二聚化激活RNA编辑),这是一个模块化的转录后合成受体平台,利用ADAR进行RNA编辑。LIDAR在不同的细胞环境中与各种受体结构兼容,能够感知多种配体并产生功能性输出。此外,LIDAR可以在同一细胞中感知正交信号并产生合成空间模式,这有可能实现复杂多细胞行为的编程。最后,LIDAR与紧凑编码兼容,可以作为合成mRNA进行递送。因此,LIDAR扩展了合成受体家族,有望推动基础研究和治疗应用的发展。