生物分离与界面分子机制创新特区研究组(18T7)卿光焱研究员团队系统总结了噬菌体展示技术在阿尔茨海默病治疗与诊断中的应用进展。
阿尔茨海默病是一种起病隐匿的进行性发展的神经退行性疾病，在临床上以记忆和认知障碍、执行功能障碍等为特征。阿尔茨海默病是全球最受关注的医疗问题之一，预计到2030年其造成的经济负担将达到2万亿美元。然而，迄今为止，尚无有效的防治策略。多肽类药物的因其具有独特的生物化学性质，例如可重复的化学合成和修饰、快速的细胞和组织渗透性以及快速的血液清除等，可作为一种极具潜力的阿尔茨海默病的治疗方法。噬菌体展示技术是最强大的药物筛选平台之一，可以对特定的靶标鉴定得到具有高亲和力和特异性多肽配体。本篇综述首次系统总结了噬菌体展示技术在阿尔茨海默病治疗与诊断中的应用进展。首先介绍了噬菌体展示的生物学概述，包括常用噬菌体的种类、噬菌体文库的构建原理、生物淘选流程、镜像噬菌体展示技术以及靶标和多肽配体多种亲和力评估方法。此外，还总结了噬菌体展示技术在阿尔茨海默病治疗、靶向药物递送和早期检测中的应用。最后，讨论了噬菌体展示技术在阿尔茨海默病中应用中存在的挑战和发展方向，并为推进其在其他神经退行性疾病中的应用进行了展望。
相关成果发表在《Theranostics》上，第一作者是18T7组职工张宪成。以上研究工作得到国家自然科学基金、我所创新特区组启动基金、兴辽英才计划等项目的支持。
Phage display derived peptides for Alzheimer's disease therapy and diagnosis
Xiancheng Zhang, Xiaoyu Zhang, Huiling Gao, Guangyan Qing*
Theranostics 2022. DOI: 10.7150/thno.68636
Alzheimer's disease (AD) is an incurable and fatal progressive neurodegenerative disorder associated with memory and cognition impairment. AD is one of the top medical care concerns across the world with a projected economic burden of $2 trillion by 2030. To date, however, there remains no effective disease-modifying therapy available. It is more important than ever to reveal novel therapeutic approaches. Peptide–based biotherapeutics has been a great potential strategy attributed to their distinct and superior biochemical characteristics, such as reproducible chemical synthesis and modification, rapid cell and tissue permeability, and fast blood clearance. Phage display, one of today’s most powerful platforms, allows selection and identification of suitable peptide drug candidates with high affinities and specificity toward target, demonstrating the potential to overcome challenges and limitations in AD diagnosis/treatment. We aim to provide the first comprehensive review to summarize the status in this research direction. The biological overview of phage display is described, including basic biology of the phage vectors and construction principle of phage library, biopanning procedure, mirror image phage display, and various binding affinity evaluation approaches. Further, the applications of phage display in AD therapy, targeted drug delivery, and early detection are presented. Finally, we discuss the current challenges and offer a future outlook for further advancing the potential application of phage display on AD and other neurodegenerative diseases.
