Targeted delivery of oligonucleotides using multivalent protein-carbohydrate interactions.
Targeted delivery of oligonucleotides using multivalent protein-carbohydrate interactions.
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DOI：
10.1039/d2cs00788f
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发表时间：
2023-02-20
影响因子：
46.2
通讯作者：
Turnbull, W. Bruce
中科院分区：
文献类型：
--
作者：
Kumar, Vajinder;Turnbull, W. Bruce
细胞表面蛋白质-碳水化合物相互作用对于病毒、某些细菌及其毒素和许多糖蛋白的组织特异性识别和内吞是必不可少的。通常蛋白质-碳水化合物相互作用是多价的-多个聚糖拷贝同时结合多聚体受体。多价性增强亲和力和结合特异性两者，并且对于将药物靶向递送至特定细胞类型是令人感兴趣的。碳水化合物介导的药物递送到达临床的第一个这样的例子是Givosiran，一种与三价N-乙酰半乳糖胺（GalNAc）配体缀合的小干扰核糖核酸（siRNA）。该配体能够通过肝细胞上的去唾液酸糖蛋白受体（ASGP-R）有效摄取核酸。ASGP-R的合成多价配体是在大约40年前多价糖科学诞生时开发的第一批“簇糖苷”之一。在这篇综述中，我们追溯了“GalNAc靶向”的历史，从早期的学术研究到目前的药物，并考虑这种递送技术的成功可能带来哪些其他机会。本文综述了利用多价碳水化合物配体将核酸靶向递送至肝细胞的发展。
Cell surface protein–carbohydrate interactions are essential for tissue-specific recognition and endocytosis of viruses, some bacteria and their toxins, and many glycoproteins. Often protein–carbohydrate interactions are multivalent – multiple copies of glycans bind simultaneously to multimeric receptors. Multivalency enhances both affinity and binding specificity, and is of interest for targeted delivery of drugs to specific cell types. The first such example of carbohydrate-mediated drug delivery to reach the clinic is Givosiran, a small interfering ribonucleic acid (siRNA) that is conjugated to a trivalent N-acetylgalactosamine (GalNAc) ligand. This ligand enables efficient uptake of the nucleic acid by the asialoglycoprotein receptor (ASGP-R) on hepatocytes. Synthetic multivalent ligands for ASGP-R were among the first ‘cluster glycosides’ developed at the birth of multivalent glycoscience around 40 years ago. In this review we trace the history of ‘GalNAc targeting’ from early academic studies to current pharmaceuticals and consider what other opportunities could follow the success of this delivery technology. This review traces the development of targeted delivery of nucleic acids to liver cells using multivalent carbohydrate ligands.
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