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].

Core Insights - The article discusses the anticipated hot research areas for the National Natural Science Foundation of China (NSFC) funding in 2026, emphasizing the importance of understanding these trends for project design [4][5]. Group 1: Core Mechanisms - Key focus areas include immune regulation (macrophage polarization, neutrophil function, T-cell exhaustion), mitochondrial function and homeostasis, novel cell death mechanisms (ferroptosis, pyroptosis), metabolic reprogramming (glycolysis, lactylation), and post-translational modifications of proteins (ubiquitination, SUMOylation) [4]. Group 2: Frontier Interdisciplinary Areas - Emerging fields highlighted are epitranscriptomics (RNA modifications like m6A, m7G), intercellular communication (exosomes), host-microbiome interactions (gut microbiota), and stem cells with regenerative medicine [5]. Group 3: Key Technologies - Important technological advancements include single-cell and spatial multi-omics, organoids and disease models, and AI/machine learning-driven target discovery and data analysis [5]. Group 4: Research Case Studies - The article presents several research cases that exemplify how researchers are engaging with these hot topics, including: - Neutrophils and their role in thrombosis, published in the European Heart Journal [12]. - Immune evasion mechanisms in tumors, published in Cell [13]. - Gut microbiota's role in Crohn's disease, published in Gut [14]. - Glycolysis and its implications in cancer, published in Signal Transduction and Targeted Therapy [14]. - Development of organoids for bone repair, published in Advanced Materials [14].