Delivery of biomacromolecules to the central nervous system (CNS) remains challenging because of the restrictive nature of the blood–brain barrier (BBB). We developed a BBB-crossing conjugate (BCC) system that facilitates delivery into the CNS through γ-secretase-mediated transcytosis. Intravenous administration of a BCC10–oligonucleotide conjugate demonstrated effective transportation of the oligonucleotide across the BBB and gene silencing in wild-type mice, human brain tissues and an amyotrophic lateral sclerosis mouse model.

中文翻译：

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静脉内施用血脑屏障交叉偶联物可促进生物大分子转运至中枢神经系统

由于血脑屏障 （BBB） 的限制性，将生物大分子递送到中枢神经系统 （CNS） 仍然具有挑战性。我们开发了一种 BBB 交叉偶联物 （BCC） 系统，该系统有助于通过 γ 分泌酶介导的转胞吞作用递送到 CNS。静脉内施用 BCC10-寡核苷酸偶联物表明，寡核苷酸在野生型小鼠、人脑组织和肌萎缩侧索硬化症小鼠模型中跨 BBB 和基因沉默有效运输。