Graduate Program in Biological Sciences, Stanford University, Stanford, CA, USA.
Department of Neurobiology, Stanford University, Stanford, CA, USA.
Nat Methods. 2018 Jul;15(7):523-526. doi: 10.1038/s41592-018-0041-z. Epub 2018 Jul 2.
Robust approaches for chemogenetic control of protein function would have many biological applications. We developed stabilizable polypeptide linkages (StaPLs) based on hepatitis C virus protease. StaPLs undergo autoproteolysis to cleave proteins by default, whereas protease inhibitors prevent cleavage and preserve protein function. We created StaPLs responsive to different clinically approved drugs to bidirectionally control transcription with zinc-finger-based effectors, and used StaPLs to create single-chain, drug-stabilizable variants of CRISPR-Cas9 and caspase-9.
稳健的化学遗传学控制蛋白质功能的方法将有许多生物学应用。我们基于丙型肝炎病毒蛋白酶开发了可稳定的多肽连接体（StaPLs）。StaPLs 会自动进行蛋白内切，默认情况下会切割蛋白，而蛋白酶抑制剂则可防止切割并保持蛋白功能。我们创建了对不同临床批准药物有响应的 StaPLs，以便使用基于锌指的效应物双向控制转录，并使用 StaPLs 构建 CRISPR-Cas9 和 Caspase-9 的单链、药物稳定的变体。
