Chemically Cross-Linked Hammerhead Ribozyme as an Efficient RNA Interference Tool

• DOI: 10.1021/jacs.3c12702
• Publication Date: 2024-02-27T18:58:40Z
• Authors: Liang-Liang Wang; Chao-Qun Wu; Qiu-Long Zhang; Yang Wang; Yan Liu; Wen-Jian Yang; Sen-Lin Ye; Yongqiang Tian; Liang Xu
• Keywords: Hammerhead ribozyme; Hairpin ribozyme; Mammalian CPEB3 ribozyme; Ligase ribozyme; VS ribozyme; DNA-directed RNA interference

RNA-cleaving ribozymes are promising candidates as general tools of RNA interference (RNAi) in gene manipulation. However, compared with other systems, such siRNA and CRISPR technologies, the ribozyme still far from broad applications on RNAi due to their poor performance cellular context. In this work, we report an efficient tool based chemically modified hammerhead (HHR). By introduction intramolecular linkage into minimal HHR reconstruct distal interaction within tertiary structure, cross-linked exhibits substrate cleavage activities almost no sequence constraint. Cellular experiments suggest that both exogenous endogenous expression can be dramatically knocked down by levels comparable those siRNA. Unlike widely applied protein-recruiting systems (siRNA CRISPR), functions solely itself great simplicity, which may provide a new approach for manipulation fundamental translational studies.