Nature子刊：尧唐生物吴宇轩等开发LNP-mRNA疗法，实现体内造血干细胞基因编辑

Core Viewpoint - The article discusses a novel approach to treating blood disorders, particularly β-thalassemia and sickle cell disease, through in vivo genome editing of hematopoietic stem cells using a lipid nanoparticle (LNP) delivery system, which eliminates the need for preconditioning and donor matching [2][3][6]. Group 1: Current Challenges in Blood Disorder Treatments - Current methods for treating blood disorders involve complex processes, including chemotherapy preconditioning and the need for high-quality hematopoietic stem cells, which limit accessibility and increase side effects [2][6]. - Virus-based gene therapy approaches face challenges such as immunogenicity, side effects, and high production costs, hindering further clinical application [2]. Group 2: Innovative Research Findings - Researchers developed a novel LNP delivery system, LNP-168, which allows for efficient targeting of hematopoietic stem cells without the need for antibody modification, enabling in vivo mRNA delivery for precise gene editing [6][7]. - The use of LNP-168 with adenine base editor (ABE8e/sgRNA mRNA) in mouse models of transfusion-dependent β-thalassemia resulted in significant increases in fetal hemoglobin levels and normalization of red blood cell morphology, indicating a potential for one-time cures [7]. Group 3: Implications for Future Treatments - The findings suggest that LNP-mRNA-based in vivo gene editing can effectively edit endogenous genes in human hematopoietic stem cells, providing a powerful and potentially curative option for blood disorders without the need for stem cell collection or mobilization [7].