Rational Design of Single‐Domain Antibodies Targeting the Central Nervous System Neurite Outgrowth Inhibitor Nogo‐A

• DOI: 10.1002/appl.70012
• Publication Date: 2025-04-28T05:15:55Z
• Authors: Vaidehi Roy Chowd...; Alexander Röntgen; Matthew Greenig; Yanira Méndez Gómez; Sebastian P. Spiegel; Magdalena Nowinska; Aubin Ramon; Pietro Sormanni; Andrew Chan; Michele Vendruscolo
• Keywords: Neurite; Rational design

ABSTRACT The oligodendrocyte‐derived membrane protein Nogo‐A is one of the most potent inhibitors neurite growth and regeneration in adult mammalian central nervous system (CNS). It has been recently shown that administration an antibody targeting promoted functional histopathological recovery animal models multiple sclerosis (MS), amyotrophic lateral (ALS), spinal cord injury (SCI) stroke. Based on these results, this study aims to develop rationally designed nanobodies target for diagnostic or therapeutic purposes, as variants offer opportunities their small size CNS penetrance. In first step our approach, we carried out computational analyses identify targetable epitopes. We then epitope‐specific CDR3 loops grafted them onto a pre‐optimised human V H scaffold create panel nanobodies. These were screened terms thermostability, solubility binding affinity towards antigen select best candidate. way, identified nanobody binds epitope within ectodomain Nogo‐A. results indicate rational design method used may facilitate initial stages development detection inhibition applications.