Antibodies and the -omics gap

The sequencing of the human genome has resulted in an explosion in the capabilities of life science. Our basic knowledge of the cell has expanded far beyond what we thought possible just a decade ago. Thanks to the advanced tools now available to study nucleic acids the opportunity to expand this knowledge further is possibly limitless. This explosion in genomics has driven developments in other similar -omics technologies such as transcriptomics and proteomics. Life scientists are consequently experiencing the very best of times for biological research.

Yet this increased knowledge is not filtering through to influence drug development. In fact over the past decade, during which our knowledge of cellular and molecular biology has intensified, the development of novel therapies has declined, and so, researchers in drug development are experiencing the worst of times.
In comparison to the speed and sensitivity available for the investigation of genomics and transcriptomics, the tools for proteomic investigation are fairly primitive. Despite advancements in proteomics to increase sensitivity and rapidity, the sensitivity of these studies is still not comparable to studies of DNA and RNA, where material can be amplified for study by PCR- they didn’t win the Nobel prize in 1993 for nothing. What’s more as antibody-based techniques are often deemed more sensitive than mass spec, many targets are verified through Western blotting or similar expression methods.
Proteins are central to the control of pretty much all cellular processes and virtually all drugs act by modulating the activity of proteins. It seems reasonable then to assume that to effectively translate genomic findings to drug development will require a toolkit that enables the manipulation of proteins with the same speed and precision that is commonplace for the manipulation of DNA and RNA. This would be a comprehensive toolkit allowing us to track, localise and modulate any protein of interest in the cell and would revolutionise our understanding of biology in health and disease. Ideally, these tools could be converted into therapeutics that could act to inhibit or activate proteins in a selective manner to overcome the aberrant protein function associated with disease.
Considering this obvious need for improved affinity reagents it is disappointing to think that the vast majority are still monoclonal antibodies produced via hybridoma technologies. Raised in animals and generated by the immortilisation of individual antibody-producing cell lines this technology has not progressed significantly since its invention almost forty years ago.
Many issues inherent in hybridoma technology have limited affinity reagents from reaching their potential- the lack of control over the selection process rendering antibodies to sensitive antigens difficult to target, the use of animals to generate material meaning scaling-up can be prohibitively expensive, the natural selection of the immune system against endogenous targets thus raising antibodies to complimentary proteins is impossible- to name but a few. These limitations from such a low-throughput technique are now particularly evident in the post genomic era.
More recently improvements have been seen in the technology of affinity reagents through the use of recombinant antibody libraries and antibody alternatives. But it seems that the familiarity of the early hybridoma libraries has everyone stuck in a rut where researchers value conservatism over innovation and consequently the research community has only a vague awareness of the advantages of alternative affinity reagents relative to the more familiar hybridoma technology.
Affimer reagents are an antibody alternative, engineered to overcome the problems that have limited researchers. They are highly stable, biochemically inert offering rapid production of highly specific binding proteins in in vitro systems they are not limited by the immune repertoire. The development of Affimer technology finally opens up the required toolkit for proteomic researchers to target the proteome with a comprehensive set of affinity reagents that may enable scientists to elucidate protein function and identify key protein–protein interactions that are involved in disease states, thus providing critical links between our vast stores of genomic data and the urgent need for new therapeutics.