北京大学伊成器团队开发新型RNA编辑平台，突破“单点编辑”，实现RNA多位点、多功能精准操控

Core Viewpoint - The article discusses the development of a new RNA editing platform called AIM (adjustable RNA information manipulation), which allows for controllable and precise manipulation of multiple nucleotides within a targeted RNA region, overcoming the limitations of existing single-point RNA editing tools [2][3]. Group 1: AIM Platform Overview - The AIM platform consists of three core components: dCas13 protein for RNA targeting, a rationally designed single-strand RNA deaminase TadA, and a specially designed loop-forming gRNA (LF-gRNA) that induces a local single-stranded "loop region" on the target RNA, exposing bases for effective editing [5][6]. - The LF-gRNA also forms a double-stranded structure with the target RNA on both sides, effectively preventing off-target editing [6]. Group 2: Editing Capabilities - The research team developed three types of AIM systems with different functionalities: AIM-A/AIM-Amax for precise A-to-I editing, AIM-C/AIM-Cmax for pure C-to-U editing, and AIM-A&C/AIM-A&Cmax for simultaneous editing of A and C within the same RNA molecule [8]. - This expansion from a single editing mode to multiple functionalities allows AIM to meet diverse RNA regulatory needs [8]. Group 3: Applications and Potential - The AIM platform demonstrated unique advantages in multi-site editing, particularly in the context of read-through of the premature stop codon UAA, where two adenine bases needed to be edited simultaneously [9]. - In cystic fibrosis cell models and Duchenne muscular dystrophy mouse models, the team observed full-length protein expression and functional recovery, showcasing the potential of AIM in disease treatment [9]. - AIM was also applied to manipulate RNA information related to post-translational modifications, allowing for regulation of protein stability through editing of key phosphorylation-related codons [9]. Group 4: Safety and Specificity - Systematic safety assessments indicated that AIM maintains a low level of off-target editing events at the RNA level and does not significantly impact global gene expression [10]. - Evaluations of potential DNA off-target risks showed no significant differences in editing levels compared to negative controls, and no immune activation responses were detected in cell and animal models, indicating high specificity and good safety of the AIM platform [10]. Group 5: Future Prospects - The AIM platform enables precise manipulation of multiple bases within specific RNA regions and expands editing modes to include A-to-I, C-to-U, and simultaneous A&C editing, while demonstrating good specificity and safety [10]. - Future applications of AIM may include precise manipulation of RNA secondary structures, translation regulatory elements, and RNA-RNA or RNA-protein interaction sites, making it an important tool for understanding and reshaping RNA functions [10].