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

Wang, Chang; Wang, Siyu; Xue, Yonger; Zhong, Yichen; Li, Haoyuan; Hou, Xucheng; Kang, Diana D; Liu, Zhengwei et al. · Nat Biotechnol · 2025

basic_science · Level V

Where this comes from

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.

Medical subject headings