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Pharmacy Information 2023
抗转铁蛋白受体抗体跨血脑屏障改造策略
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Abstract:
实现有效的跨血脑屏障递送是开发治疗中枢神经系统疾病药物的关键一步，特别是近几年发展迅速的生物药物，如抗体、核酸药物和酶等，在给药以后，这些生物大分子基本上无法进入大脑，需要开发高效的跨脑转运系统。研究人员发现脑毛细血管内皮细胞上的一些转运蛋白具有药物递送的潜力，转铁蛋白受体1(Transferrin receptor 1, TfR1)就是其中之一，多家医药公司或研究机构基于TfR1的跨BBB递送平台开发出了中枢神经系统疾病的治疗药物已经被批准上市或正在进行临床实验，这激发了脑部靶向药物的研发。本文旨在讨论具有跨BBB递送的TfR1抗体的改造，从而为高脑转运效率的TfR1抗体递送平台的开发提供理论基础。
Effective delivery across the blood-brain barrier is a key step in the development of drugs for the treatment of central nervous system diseases. In particular, as the rapid development of biologic drugs in recent years, such as antibodies, nucleic acid drugs and enzymes, after administration, these biomacromolecules are basically unable to enter the brain, so it is necessary to develop an efficient trans-brain transport system. Researchers have found that some transporters on brain capillary endothelial cells have drug delivery potential, and transferrin receptor 1 (Transferrin receptor 1, TfR1) is one of them. Several pharmaceutical companies or research institutions have developed drugs for the treatment of central nervous system diseases based on the trans-BBB delivery platform of TfR1, which have been approved or are undergoing clinical trials. This has spurred the development of targeted drugs for the brain. This paper aims to discuss the modification of TfR1 antibodies with trans-BBB delivery, so as to provide a theoretical basis for the development of a TfR1 antibody delivery platform with high brain transport efficiency.
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