Wang Chang, Wang Siyu, Xue Yonger, Zhong Yichen, Li Haoyuan, Hou Xucheng, Kang Diana D, Liu Zhengwei, Tian Meng, Wang Leiming, Cao Dinglingge, Yu Yang, Liu Jayce, Cheng Xiaolin, Markovic Tamara, Hashemi Alice, Kopell Brian H, Charney Alexander W, Nestler Eric J, Dong Yizhou
Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Biotechnol. 2024 Nov 25. doi: 10.1038/s41587-024-02487-7.
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.
由于血脑屏障（BBB）的限制性，将生物大分子递送至中枢神经系统（CNS）仍然具有挑战性。我们开发了一种血脑屏障穿越偶联物（BCC）系统，该系统通过γ-分泌酶介导的转胞吞作用促进向中枢神经系统的递送。静脉注射BCC10-寡核苷酸偶联物证明寡核苷酸能有效穿过血脑屏障，并在野生型小鼠、人脑组织和肌萎缩侧索硬化小鼠模型中实现基因沉默。
