肿瘤细胞治疗研究
英文原题：Base editing for precision therapeutics.
碱基编辑（BE）能够在不诱导双链断裂的情况下，在DNA或RNA中精确引入单核苷酸改变，对于校正单核苷酸变异具有重要的治疗前景，而单核苷酸变异占已知致病遗传变异的一半以上。
碱基编辑（BE）能够在不诱导双链断裂的情况下精确引入DNA或RNA的单核苷酸改变，对于纠正单核苷酸变异具有重大治疗前景，而单核苷酸变异占已知致病遗传变异的一半以上。近年来的进展提高了碱基编辑器的特异性、效率和递送能力，使临床导向的操作成为可能。在临床上，BE已在镰状细胞病、β-地中海贫血、白血病（通过CAR T和表位工程）、高胆固醇血症（PCSK9和ANGPTL3）、α-1-抗胰蛋白酶缺乏症以及Ia型糖原贮积病中显示出早期成功或强大的转化前景。剩余的关键挑战包括活性窗口内的旁观者编辑、残留的脱靶DNA和RNA编辑、递送限制（载荷大小、组织靶向和重复给药限制）、免疫原性，以及在相关细胞类型和疾病背景下对持久长期安全性证据的需求。持续的技术改进、严谨的临床前验证和严格的临床评估对于充分实现BE在精准医学中的变革性潜力至关重要。
Base editing (BE), the precise installation of single-nucleotide changes in DNA or RNA without inducing double-strand breaks, holds substantial therapeutic promise for correcting single-nucleotide variants, which constitute more than half of the known pathogenic genetic variants. Recent advances have improved base editor specificity, efficiency, and delivery, enabling clinically oriented procedures. Clinically, BE has shown early success or strong translational promise in sickle cell disease, -thalassemia, leukemia (via CAR T and epitope engineering), hypercholesterolemia (PCSK9 and ANGPTL3), alpha-1-antitrypsin deficiency, and glycogen storage disease type Ia. Key remaining challenges include bystander editing within the activity window, residual off-target DNA and RNA editing, delivery constraints (payload size, tissue targeting, and redosing limits), immunogenicity, and the need for durable long-term safety evidence across relevant cell types and disease contexts. Continued technological refinements, careful preclinical validation, and rigorous clinical assessment will be essential to fully realize BE's transformative potential in precision medicine.
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