Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB, Eindhoven, The Netherlands.
Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, 2629 HZ, Delft, The Netherlands.
Angew Chem Int Ed Engl. 2022 Jun 27;61(26):e202202436. doi: 10.1002/anie.202202436. Epub 2022 Apr 26.
Protocells containing enzyme-driven biomolecular circuits that can process and exchange information offer a promising approach for mimicking cellular features and developing molecular information platforms. Here, we employ synthetic transcriptional circuits together with CRISPR/Cas-based DNA processing inside semipermeable protein-polymer microcompartments. We first establish a transcriptional protocell that can be activated by external DNA strands and produce functional RNA aptamers. Subsequently, we engineer a transcriptional module to generate RNA strands functioning as diffusive signals that can be sensed by neighboring protocells and trigger the activation of internalized DNA probes or localization of Cas nucleases. Our results highlight the opportunities to combine CRISPR/Cas machinery and DNA nanotechnology for protocellular communication and provide a step towards the development of protocells capable of distributed molecular information processing.
包含酶驱动生物分子电路的原细胞可以处理和交换信息，为模拟细胞特征和开发分子信息平台提供了有前途的方法。在这里，我们在半透性蛋白质-聚合物微室中使用合成转录电路和基于 CRISPR/Cas 的 DNA 处理。我们首先建立了一个转录原细胞，它可以被外部 DNA 链激活，并产生功能性 RNA 适体。随后，我们设计了一个转录模块，生成作为扩散信号的 RNA 链，这些信号可以被邻近的原细胞感知，并触发内化的 DNA 探针的激活或 Cas 核酸酶的定位。我们的结果突出了将 CRISPR/Cas 机制和 DNA 纳米技术结合用于原细胞通信的机会，并为开发能够进行分布式分子信息处理的原细胞迈出了一步。
