Guo Chipeng, Tang Yingsen, Zeng Ling, You Xiaomei, Luo Siweier, Du Yufei, Wang Le, Wang Liangchun, Wang Jianchuan, Chen Jinjin, Zhou Yiming
Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
Basic and Translational Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
Adv Sci (Weinh). 2025 Jun;12(21):e2501628. doi: 10.1002/advs.202501628. Epub 2025 Apr 7.
The hyperactivation of autoreactive B cells and plasma cells leads to the development of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), therefore, targeting the abnormal B cells and plasma cells might hold promise for the treatment of these refractory and relapsing diseases. This study developed lipid nanoparticle-encapsulated mRNA-encoding antibodies (mRNab-LNPs) targeting CD19, and evaluated their therapeutic efficacy in lupus and RA mice. mRNab-LNPs enabled robust production of anti-CD19 antibodies in multiple cell lines in vitro. Interestingly, intramuscular injection of mRNab-LNPs resulted in high and sustained production of anti-CD19 antibodies in mice. In particular, the numbers of CD19+ circulating B cells and tissue-resident plasma cells are significantly reduced by mRNab-LNPs in mice. As a result, mRNab-LNPs significantly reduced the histopathological changes and tissue injuries in both lupus and RA mice. Collectively, these findings demonstrate the therapeutic and translational potential of mRNab-LNPs in the treatment of SLE and RA.
自身反应性B细胞和浆细胞的过度活化会导致系统性红斑狼疮（SLE）和类风湿性关节炎（RA）的发生，因此，针对异常的B细胞和浆细胞可能为治疗这些难治性和复发性疾病带来希望。本研究开发了靶向CD19的脂质纳米颗粒包裹的编码抗体的mRNA（mRNab-LNPs），并评估了它们在狼疮和类风湿性关节炎小鼠模型中的治疗效果。mRNab-LNPs能够在体外多种细胞系中强劲产生抗CD19抗体。有趣的是，肌肉注射mRNab-LNPs能使小鼠体内产生高且持续的抗CD19抗体。特别是，mRNab-LNPs显著减少了小鼠体内CD19+循环B细胞和组织驻留浆细胞的数量。结果，mRNab-LNPs显著减轻了狼疮和类风湿性关节炎小鼠的组织病理学变化和组织损伤。总的来说，这些发现证明了mRNab-LNPs在治疗SLE和RA方面的治疗潜力和转化潜力。
