The lack of effective treatments for brain disorders related to NMDA receptor hypofunction, such as schizophrenia and GRIN1-related disorders, has long been a major challenge in the medical field. Traditional small-molecule drugs often lack selectivity and exhibit significant side effects, while antibody-based therapies struggle to cross the...
The lack of effective treatments for brain disorders related to NMDA receptor hypofunction, such as schizophrenia and GRIN1-related disorders, has long been a major challenge in the medical field. Traditional small-molecule drugs often lack selectivity and exhibit significant side effects, while antibody-based therapies struggle to cross the blood-brain barrier (BBB), limiting their efficacy.To address this clinical need, a collaborative effort involving the Institute of Functional Genomics in Montpellier (France), the Department of Pharmacology and Toxicology at the University of Toronto (Canada), and the Faculty of Health, Medicine, and Technology at Paris-Saclay University (France) has developed a bivalent bispecific nanobody named DN13-DN1. Administered via intraperitoneal (IP) injection, this nanobody successfully crosses the BBB, specifically binds to and enhances the activity of the mGlu2 receptor. In two mouse models of NMDA receptor hypofunction—neonatal PCP-induced (mimicking schizophrenia) and GluN1-KD genetic (mimicking GRIN1 disorder)—DN13-DN1 significantly improved cognitive deficits and sensorimotor gating impairments. Subchronic treatment demonstrated stable therapeutic effects without noticeable side effects, outperforming both traditional small-molecule drugs and IgG-class antibodies. This study was published in the leading academic journal Nature. Let’s delve into the details.
在现代医学诊断与生命科学研究中，蛋白质作为直接关联疾病表型的关键生物标志物，其精准、快速检测具有重要意义。传统检测技术却面临诸多局限，如ELISA等免疫测定方法，或需繁琐的分离洗涤步骤，或依赖成对抗体的苛刻条件，难以满足即时检测与高通量分析的需求；质谱分析虽为蛋白质组研究的“金标准”，却依赖大型昂贵设备且分析流程冗长。
在人类与病毒的漫长斗争中，病毒的持续变异如同一场“道高一尺，魔高一丈”的军备竞赛。新冠疫情的阴霾逐渐散去之时，我们仍未完全摆脱冠状病毒带来的威胁，新的病毒变异株不断涌现，给全球公共卫生安全持续带来挑战。在此背景下，由匹兹堡大学等多个世界知名机构组成的科研团队，通过创新的技术手段，从免疫后的羊驼体内成功筛选出一种具有“超级免疫力”的泛沙贝科病毒纳米抗体(pan-sarbecovirus nanobodies,psNbs)。该研究发表于《Cell Reports》，旨在找到一类能够对抗整个病毒家族的通用解决方案。
在植物生物学研究中，解析蛋白质的定位、互作及动态变化是揭示生命机制的核心。传统蛋白标记技术依赖荧光蛋白或表位标签，但常因标签尺寸过大、亲和力不足或适用场景有限而受阻。尤其对于多跨膜蛋白（如金属转运蛋白）、功能敏感蛋白等“难标记蛋白”，传统方法易破坏其结构与功能，导致研究停滞。纳米抗体作为一种具有亲和力高、可基因组编码等优势的小分子抗体，为突破这一瓶颈提供了可能。此前，ALFA标签与ALFA纳米抗体系统已在动物、酵母中展现卓越性能，但其在植物中的适用性尚未系统评估。
如今，纳米抗体已在生物医药、疾病诊断、临床治疗及工农业等多个领域展现出重要的价值。而优质的纳米抗体的发现服务则离不开离不开一只拥有“零免疫背景”的羊驼，更离不开一只经过了科学管理及饲养的健康羊驼。纳博生命作为一家提供从羊驼免疫到抗体发现及抗体工程，再到体内外验证全流程服务的科技公司，自成立之初便高度重视羊驼的标准化管理。