纳米抗体及其在诊断检测中的研究进展

Progress in nanobody and its application in diagnosis

摘要:

骆驼血液中存在天然缺失轻链的重链抗体，克隆该重链抗体的可变区得到最小的抗原结合片段，即纳米抗体 (Nanobody，Nb)。Nb的单域性质使其较普通抗体具有一些独特性能，比如高度水溶性和构象稳定性，较强的抗原亲合力和优良的组织穿透能力，容易体外表达和人源化改造修饰等，使其在诊断检测领域展现出广阔的应用前景。尽管Nb的应用开发已经取得前所未有的成功，技术上仍然有待进一步优化，其中包括噬菌体纳米抗体库构建以及Nb的胶体金标记分析等技术。文中简单介绍Nb的研究进展，并从Nb制备、在疾病的体外检测以及体内肿瘤无创伤影像诊断领域的应用3个方面，讨论进一步提高Nb亲合力和人源化改造等优化Nb分子特征的策略，分析Nb在疾病检测诊断应用中存在的问题，并提出一些积极的应对方案。

Abstract:

Nanobodies are derived from the vari-able domain of the heavy-chain antibodies (HCAbs) that occur naturally in the serum of Camelidae. They are the smallest antibody fragments capable to bind antigens. With the characteristics of their increased solubility, increased domain stabilities, nanomolar affinities, easy crossing the blood-brain barrier, easy generation, engineering, optimization and tailoring, easy humanization, nanobodies have extensive application prospects in diagnosis and detection. Although nanobody has demonstrated tremendous success, a number of practical challenges limit its broader applications in disease diagnosis and detection, including construction of a phage library and selection of nanobody fragments with high affinity and immunogold labeling technique. Here, we review several recent findings on the use of nanobodies in molecular diagnostics and suggest some practical strategies in resolving the current challenges in this attractive research area, particularly to optimize the affinity, solubility, humanization of nanobodies.