To date vNAR application as therapeutics has focussed upon extracellular targets, with vNARs isolated against proteins ranging from ICOSL for use in uveitis, TNF-α in polyarthritis, and AMA1 in malaria, to a variety of potential tumour targets including Her2, DLL4 and PD-1 (Kovaleva et al., 2017; Ubah et al., 2017; 2019; Feng et al., 2019; English et al., 2020; Leach et al., 2020). Here, ICOSLG is linked to polyarticular arthritis.