Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA; Department of Chemistry, Emory University, Atlanta, GA, USA.
Trends Biotechnol. 2021 Dec;39(12):1289-1307. doi: 10.1016/j.tibtech.2021.03.007. Epub 2021 May 10.
Nucleic acid therapeutics (NATs) hold promise in treating undruggable diseases and are recognized as the third major category of therapeutics in addition to small molecules and antibodies. Despite the milestones that NATs have made in clinical translation over the past decade, one important challenge pertains to increasing the specificity of this class of drugs. Activating NATs exclusively in disease-causing cells is highly desirable because it will safely broaden the application of NATs to a wider range of clinical indications. Smart NATs are triggered through a photo-uncaging reaction or a specific molecular input such as a transcript, protein, or small molecule, thus complementing the current strategy of targeting cells and tissues with receptor-specific ligands to enhance specificity. This review summarizes the programmable modalities that have been incorporated into NATs to build in responsive behaviors. We discuss the various inputs, transduction mechanisms, and output response functions that have been demonstrated to date.
核酸疗法（NATs）在治疗难以治疗的疾病方面具有广阔的前景，被认为是继小分子和抗体之后的第三大治疗类别。尽管过去十年中 NATs 在临床转化方面取得了里程碑式的进展，但一个重要的挑战是提高这类药物的特异性。仅在致病细胞中激活 NATs 是非常理想的，因为它将安全地拓宽 NATs 在更广泛的临床适应症中的应用。智能 NATs 通过光解笼反应或特定的分子输入（如转录本、蛋白质或小分子）触发，从而补充了目前用受体特异性配体靶向细胞和组织以提高特异性的策略。本综述总结了已被整合到 NATs 中的可编程模式，以构建响应行为。我们讨论了迄今为止已经证明的各种输入、转导机制和输出响应功能。
