Student Posters 51st Lorne Proteins Conference 2026

   Enhancing the plasma half-life of broad-spectrum chemokine binding tick proteins by fusion to XTEN tags for use as anti-inflammatory drugs   (#103)

Mikaela Bell 1 , Pramod Aryal 1 2 , Shankar Devkota 3 , Harley Robinson 4 , Simon Foster 4 , Ram Bhusal 1 , Barb Kemp-Harper 1 , Martin Stone 1
  1. Monash University, Clayton, VICTORIA, Australia
  2. Onko Innate, Melbourne
  3. University of Adelaide, Adelaide
  4. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

Evasins are a family of >50 chemokine binding anti-inflammatory proteins identified in the saliva of some species of ticks. EVA-ACA1001, EVA-P974 and EVA-AAM1001 have been identified as promiscuous CC chemokine binders with affinity for almost all CC chemokines. We believe their promiscuity makes them a promising potential treatment for inflammatory diseases. As evasins are small proteins (~13kDa) their half-life in vivo is of critical concern for drug development. Despite this, very little is known about their pharmacokinetics. To improve the half-life of evasins we have produced fusion proteins using the XTEN fusion partner, originally developed by Schellenberger et al. XTEN is an unstructured polypeptide chain that can be produced at various lengths to scale the hydrodynamic volume of the protein of interest. Here we detail the expression, purification, functional validation, and pharmacokinetic analysis of three different length XTEN fusion to our evasins of interest.

  1. Bhusal RP, Eaton JRO, Chowdhury ST, Power CA, Proudfoot AEI, Stone MJ, et al. Evasins: Tick Salivary Proteins that Inhibit Mammalian Chemokines. Trends Biochem Sci. 2020;45(2):108-22.
  2. Bhusal RP, Aryal P, Devkota SR, Pokhrel R, Gunzburg MJ, Foster SR, et al. Structure-guided engineering of tick evasins for targeting chemokines in inflammatory diseases. Proceedings of the National Academy of Sciences. 2022;119(9):e2122105119
  3. Podust VN, Balan S, Sim BC, Coyle MP, Ernst U, Peters RT, et al. Extension of in vivo half-life of biologically active molecules by XTEN protein polymers. J Control Release. 2016;240:52-66.