The variable lymphocyte receptor as an antibody alternative

Variable lymphocyte receptors (VLRs) are leucine-rich repeat proteins in jawless vertebrates that function similarly to Ig antibodies. However, VLRs possess a distinct crescent-shaped structure and modularity that results in a concave binding interface that contrasts significantly with Ig antibodies. Antigen binding interactions result in specific, high affinity VLR binding interactions with both proteins and glycans. The natural sourcing of VLRs allows for immunization strategies, while the modularity enables a whole host of protein engineering approaches including consensus scaffolds, designed libraries and directed evolution with display technologies. VLR technologies have been recently deployed for applications in cell-specific targeting, drug delivery, tumor diagnostics and even protein stabilization. It is anticipated that the VLR field will continue to emerge to provide unique solutions for targeting glycans, evolutionarily conserved proteins and cellular specificity.