Intravenous administration of blood–brain barrier-crossing conjugates facilitate biomacromolecule transport into central nervous system

IF 33.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2024-11-25 DOI:10.1038/s41587-024-02487-7

Chang Wang, Siyu Wang, Yonger Xue, Yichen Zhong, Haoyuan Li, Xucheng Hou, Diana D. Kang, Zhengwei Liu, Meng Tian, Leiming Wang, Dinglingge Cao, Yang Yu, Jayce Liu, Xiaolin Cheng, Tamara Markovic, Alice Hashemi, Brian H. Kopell, Alexander W. Charney, Eric J. Nestler, Yizhou Dong

引用次数: 0

Abstract

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.

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静脉注射可跨越血脑屏障的共轭物，促进生物大分子向中枢神经系统的转运

由于血脑屏障（BBB）的限制性，向中枢神经系统（CNS）输送生物大分子仍然具有挑战性。我们开发了一种跨血脑屏障共轭物（BCC）系统，可通过γ-分泌酶介导的转囊作用将生物大分子送入中枢神经系统。静脉注射 BCC10-寡核苷酸共轭物后，野生型小鼠、人类脑组织和肌萎缩性侧索硬化症小鼠模型中的寡核苷酸均能有效穿越 BBB，并实现基因沉默。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

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