Nature连发4篇论文，揭开这种RNA编辑酶在自身免疫疾病中的作用

Core Insights - The ADAR (Adenosine deaminases acting on RNA) family plays a crucial role in RNA A-to-I editing, regulating RNA diversity, immune homeostasis, and neural function [3] - ADAR-based RNA editing technology has rapidly developed, offering advantages over CRISPR gene editing, such as avoiding the introduction of foreign editing enzymes and related immunogenicity issues, making it a promising candidate for genetic disease therapies [3] - Mutations in the ADAR1 gene can lead to autoimmune diseases, such as Aicardi-Goutières syndrome, by editing the host's double-stranded RNA (dsRNA) to prevent unnecessary autoimmune responses [3] Research Findings - A series of studies published in Nature in July 2022 elucidated the downstream pathways of ADAR1 gene mutations leading to autoinflammation, identifying ZBP1 as a key effector factor in cell death and inflammation transcription [4][6] - Research from Stanford University highlighted that ADAR1-mediated RNA A-to-I editing is a critical post-transcriptional event preventing innate immune interferon responses triggered by self dsRNA, with reduced editing levels due to genetic factors increasing the risk of inflammatory diseases [8] - A study published in Nature Cancer in February 2025 identified ADAR1 as a druggable target in prostate cancer, leading to the development of the small molecule inhibitor ZYS-1, which demonstrated significant anti-tumor effects and good safety profiles [9] Drug Development and Applications - Extensive research indicates that ADAR1 is not only an RNA editing enzyme but also closely related to autoimmune diseases and cancer, making it an important drug target [12] - Strategies for developing ADAR1-targeted inhibitors include targeting its catalytic domain, regulating upstream and downstream signaling pathways, and employing PROTAC degradation technology, showing broad prospects in treating cancer and autoimmune diseases [12] - A live lecture organized by BioWorld and Yi Qiao Shen Zhou will discuss the role of ADAR-mediated RNA editing in cancer therapy and the significance of ADAR1 as a drug target, featuring insights from experts in the field [12]