16 April 2019

Amyloid fibrils are misfolded proteins which have assembled to form insoluble aggregates in the form of fibers that are resistant to degradation. Amyloid formation is often associated with a disease that is specific to the proteins or localisation of the aggregate. Well known examples of amyloid diseases include Alzheimer’s disease, Diabetes type 2 and the spongiform encephalopathies (1). The precise molecular mechanism(s) by which these different proteins/peptides self-assemble and how the assembly process results in disease remain unclear (2).

Dr. David Bunka is the Co-founder and Chief Technical Officer (CTO) of the Aptamer Group. David holds a Ph.D. in Molecular Biology and has spent nearly 20 years developing DNA and RNA nucleic acid aptamers against a wide variety of targets including small molecules, proteins, viruses, whole cells and tissue biopsies. While at the University of Leeds David worked with one of the world leading research groups on protein folding and misfolding in amyloid diseases; headed by Professor Sheena Radford FRS, FMedSci. This work resulted in a paper entitled Distinguishing closely-related amyloid precursors using an RNA aptamer for the Journal of Biological Chemistry on which David is a co-author.

In this study, automated in vitro selection was used to identify a 2′fluoro-modified RNA aptamer able to preferentially bind to the full-length hβ2m (compared to the ΔN6 truncation mutant) and alter fibril assembly. The hβ2m specific aptamer was minimized to a 44-nucleotide-long fragment and both aptamers binding interface, affinity, and specificity for hβ2m were determined by Surface Plasmon Resonance (SPR), fluorescence spectroscopy, and Nuclear Magnetic Resonance (NMR).  The minimized fragment was able to affect the co-aggregation of hβ2m and ΔN6.

In conclusion, the biophysical and biochemical studies presented demonstrate that RNA aptamers can be highly specific and discriminatory probes, modulating co-polymerization reactions and controlling the course of amyloid assembly. Discrimination between the different assembly precursors offers an opportunity to alter the course of co-assembly and to decipher the mechanisms of protein assembly into amyloid to inform the design of therapeutic/diagnostic strategies able to target individual amyloid precursors (3).

Sarell CJ, Karamanos TK, White SJ, Bunka DH, Kalverda AP, Thompson GS, Barker AM, Stockley PG, Radford SE. (2014).  Distinguishing closely related amyloid precursors using an RNA aptamer. J Biol Chem. 2014 Sep 26;289(39):26859-71.



  1. Rambaran, R., Serpell, L., Amyloid fibrils: Abnormal protein assembl Prion. 2008 Jul-Sep; 2(3): 112–117.
  2. Berthelot K., Cullin C., Lecomte S. (2013) What does make an amyloid toxic: morphology, structure or interaction with membrane? Biochimie 95, 12–19.
  3. Lu J. X., Qiang W., Yau W. M., Schwieters C. D., Meredith S. C., Tycko R. (2013) Molecular structure of β-amyloid fibrils in Alzheimer’s disease brain tissue. Cell 154, 1257–1268

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