Aptamers were the first generation of non-antibody affinity reagents, and have had some success – a therapy, Pegaptinib, marketed as Macugen and a biomarker discovery/validation platform called SOMAscan. However, despite over $2Bn investment, the success of aptamers has been limited. This is probably due to a number of shortcomings.
The most obvious of these is that aptamers are physically limited to a small range of conformations, and chemically limited in the type of bonds that can be formed. Their highly charged backbone is self-repelling, making conformational stability difficult, yet it non-specifically binds numerous proteins, making specificity and high background a problem. These limitations, and a limited range of building blocks has meant that aptamers have ultimately fallen far short of what was initially hoped for.
Although the RNA world hypothesis (that nucleic acids formed the basis for the evolution of life) appears to be a seductive rationale for the development of libraries of nucleic acids and their screening for protein binders, the reality is that life is protein mediated, and protein-protein interactors will always be easier to identify – a key fact in the development of Affimer technology.
Sensitivity to the assay environment has been solved because the Affimer scaffold has evolved to be resistant to a wide pH range, making it suitable for an equally wide range of assay conditions. Affimer molecules are also not sensitive to EDTA (a problem for aptamers that require Mg++ for folding and function).
The Affimer scaffold has been engineered so that it no longer binds to proteins found in human cells, serum or plasma. The Biological half-life of Affimer molecules is also superior because they are biologically and biophysically stable. Affimer proteins are chemically diverse, already having a peptide backbone and 19 naturally occurring amino acid side chains.
From a business perspective Affimer products are not easily reverse-engineered and Avacta Life Sciences owns the scaffold intellectual property rights (IPR) and has licensed all necessary screening IPR.