Authors: Scarlett J. Barker, Mai B. Thayer, Chaeyoung Kim, David Tatarakis, Matthew J. Simon, Rebekah Dial, Lizanne Nilewski, Robert C. Wells, Yinhan Zhou, Megan Afetian, Padma Akkapeddi, Alfred Chappell, Kylie S. Chew, Johann Chow, Allisa Clemens, Claire B. Discenza, Jason C. Dugas, Chrissa Dwyer, Timothy Earr, Connie Ha, Yvonne S. Ho, David Huynh, Edwin I. Lozano, Srini Jayaraman, Wanda Kwan, Cathal Mahon, Michelle Pizzo, Yaneth Robles-Colmenares, Elysia Roche, Laura Sanders, Alexander Stergioulis, Raymond Tong, Hai Tran, Y. Zuchero, Anthony A. Estrada, Kapil Gadkar, Christopher M. M. Koth, Pascal E. Sanchez, Robert G. Thorne, Ryan J. Watts, Thomas Sandmann, Lesley A. Kane, Frank Rigo, Mark S. Dennis, Joseph W. Lewcock, Sarah L. DeVos
Published: 2024-08-14
DOI: 10.1126/scitranslmed.adi2245
Source: Full article
Antisense oligonucleotides (ASOs) are promising therapeutics for treating various neurological disorders. However, ASOs are unable to readily cross the mammalian blood-brain barrier (BBB) and therefore need to be delivered intrathecally to the central nervous system (CNS). Here, we engineered a human transferrin receptor 1 (TfR1) binding molecule, the oligonucleotide transport vehicle (OTV), to transport a tool ASO across the BBB in human TfR knockin (TfR