Beyond the aptamer

Aptamers have been hailed as a new class of molecules with great potential to rival monoclonal antibodies in therapeutic, diagnostic, analytical as well as basic research applications.

Described just over two decades ago, the field of aptamer technology received a great boost in 2004 after the first FDA approved drug, Macugen, to treat age related macular degeneration, and later the development of the first aptamer based diagnostic platform for the analysis of mycotoxins in grain. Yet these molecules have not received the anticipated level of interest or resulted in a change in the majority of researchers’ methodologies, with antibodies holding the prime spot as the go-to affinity reagent.
This is in part due to the long and established history of antibodies as research reagents – the utilisation of antibodies for their molecular recognition in biological research predates the 1950s. Yet the many limitations of antibodies have long frustrated researchers and resulted in the retraction of published manuscripts, consequently creating a demand for improved affinity reagents.
Aptamers supposedly offer increased stability and the opportunity to develop binding molecules to theoretically any molecule, without the immune system limitations previously posed by antibodies, so why haven’t they gained increased usage by researchers?
It seems researchers have come to accept a level of cross-reactivity or under-performance from antibodies, with an attitude of ‘as long as I can see my protein, a bit of cross-reactivity is OK’ being standard, whilst more may be expected from any new technology.
The majority of aptamers are considered to be bespoke reagents, isolated with a very specific function in mind, and while cross-reactivity can be selected for or against as needed with relative ease, it is very difficult to use these reagents with successfully in an off-the-shelf manner, outside of the labs in which they were generated.
In reality both great antibodies and great aptamers are highly specific. Yet both classes of reagent suffer from the binding of molecules to surfaces other than the recognition surface: the constant region of antibodies interacts with all kinds of immune system effector molecules while the sugar-phosphate backbone of a nucleic acid gets bound by all kinds of RNA and DNA binding proteins.
Handily, the Affimer scaffold has been engineered to abolish all its interactions with human proteins, removing this problem and ultimately providing better signal-to-noise ratio in protein detection, so Affimer reagents can be used off-the-shelf. They bind with high affinity and specificity to 3D targets making them ideal for functional studies, where their properties of being biochemically inert and experimentally robust allow their optimal performance.
Equally if you want something more specialised we are able to take the customers validation considerations into account as part of our selection process. We can adapt processes to ensure that custom products are raised under your end-use conditions; in essence, making the intended ‘end validation’ part of our selection process. This allows us to develop and validate the product according to your specifications and delivered to your lab within just 7 weeks.