Delivery of small interfering RNA and antisense oligonucleotides across the blood-brain barrier with monovalent transferrin receptor 1 binding VHH-Fc fusion proteins

Ian J. Huggins Michele Carrer Jinro A. Santos Michael A. Fazio Bret Holguin Stevee Phi Thazha P. Prakash Megan Afetian M. A. Bakooshli Stephanie K. Klein Rodrigo Galindo-Murillo Andrew A. Rodriguez Fredrik Kamme Hans J. Gaus A. Chappell M. Bravo-Hernández A. Pinto-Duarte Ryan Quinones G. Jacquot Marion David Frank Rigo Holly Kordasiewicz Hien T. Zhao P. Jafar-nejad M. Tanowitz Eric E. Swayze

Aug 2026 · bioRxiv · 0 citations · 74 references

Biology

TL;DR

A novel monovalent TfR1-binding VHH-Fc is described for the delivery of oligonucleotide cargo, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) across the BBB in rodents and non-human primates (NHPs), supporting the translational potential of the VHH-antisense RMT platform for the treatment of neurological disorders.

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