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Nanobodies raised against the cytotoxic α-synuclein oligomer are oligomer-specific and promote its cellular uptake
npj Biosensing 2025
Janni Nielsen, Jannik N. Pedersen, Giulia Kleijwegt, Jan S. Nowak, D. Otzen et all.
This study developed and characterized two nanobodies (NB1, NB2) raised against the cytotoxic α-synuclein oligomer, showing they are oligomer-specific, distinguish the toxic oligomer from monomeric α-synuclein, and promote its cellular uptake. Flow Induced Dispersion Analysis (FIDA) was used to measure the solution-phase binding affinity of the nanobodies to the oligomer by tracking the hydrodynamic-radius change of the labeled nanobodies, giving KD ~31 nM (NB1) and ~41 nM (NB2) and confirming no binding to monomer — corroborating SPR. It is an example of using FIDA to measure nanobody binding affinity and target selectivity in solution.
