造血干细胞基因编辑产生的B淋巴细胞蛋白工厂，这一成果由洛克菲勒大学
在这项研究中，研究组报道了一种替代的基因编辑方法，将少量造血干细胞和祖细胞（HSPCs）主题化，以指导抗体或货物蛋白的长期、高水平表达。在小鼠中，来自移植的HSPCs的编辑过的B淋巴细胞被同源抗原激活，进行克隆扩增，并发育成特异性抗体合成或货物蛋白合成浆细胞。这些细胞产生持久的、治疗水平的抗HIV-1、疟疾或抗流感病毒bNAb的血清抗体，介导对异源病毒致命攻击的普遍保护。他们的数据为细胞治疗方法提供了一个范例，以预防或治疗疾病主题的自我扩增B细胞蛋白工厂。
据了解，治疗性蛋白的长期体内生产和疫苗的开发，可引发针对主要病原体的广泛中和抗体（bNAbs）的保护水平，面临着挑战。
附：英文原文
Title: B lymphocyte protein factories produced by hematopoietic stem cell gene editing
Author: Harald Hartweger, Chiara Ruprecht, Kai-Hui Yao, Philippe Laffont, Gabriella Lima Dos Reis, Pengcheng Zhou, Thomas Hgglf, Laurine Binet, Maximilian Loewe, Jun P. Hong, Tianli Xiao, Esen Sefik, Brianna Hernandez, Anna Gazumyan, Mila Jankovic, Michael S. Seaman, Giulia Costa, Sean A. Nelson, Jordan Clark, Sachie Kanatani, Patrick C. Wilson, Florian Krammer, Elena A. Levashina, Jean-Philippe Julien, Hedda Wardemann, Photini Sinnis, Leonidas Stamatatos, Richard A. Flavell, Michel C. Nussenzweig
Issue&Volume: 2026-04-16
Abstract: Long-term in vivo production of therapeutic proteins and development of vaccines that elicit protective levels of broadly neutralizing antibodies (bNAbs) against major pathogens face challenges. In this study, we report on an alternative gene editing approach using small numbers of hematopoietic stem and progenitor cells (HSPCs) to direct long-term, high-level expression of antibodies or cargo proteins. In mice, edited B lymphocytes derived from transplanted HSPCs were activated by cognate antigen, underwent clonal expansion, and developed into specific antibody-synthesizing or cargo protein–synthesizing plasma cells. These cells produced long-lasting, therapeutic levels of serum antibody against HIV-1, malaria, or an anti-influenza virus bNAb that mediated universal protection from heterologous lethal challenge. Our data provide a paradigm for cell therapy approaches to prevent or treat disease using self-amplifying B cell protein factories.
DOI: adz8994
Source: https://www.science.org/doi/10.1126/science.adz8994