The lack of antibody specificity has now been recognized as the major cause of antibody failure. A recent survey by 1DegreeBio with 400 antibody users suggests that 50% of commercial antibodies does not work as expected. Emerge Biotech revolutionizes the development of monoclonal antibodies by interrogating their specificity and affinity at early stages of antibody development. The principal innovation, the genetic depletion of antibody targets, provides an unambiguous approach to isolate specific antibodies.
Why is it important to develop antibodies?
Antibodies are key molecules in the defence against diseases. They are produced by specific cells of our immune system, termed B lymphocytes, for instance in response to evading pathogens, like viruses or bacteria. An important feature of antibodies helps us to use these molecules for the diagnosis of diseases: they recognize and bind to specific proteins. Antibodies can thus be used to examine whether a tissue sample, like a biopsy is diseased, in case a specific protein is altered during disease. Therefore antibodies are manufactured at large scale for the diagnosis and therapy of diseases in the clinic.
What are challenges to manufacturing antibodies?
Most commercial antibodies are produced by immunizing an animal host with synthetic proteins or peptides. These molecules may be distinct from the natural repertoire of proteins. For instance, an antibody raised against a synthetic protein may not recognize the natural analogue or even worse, it may recognize more than one protein. This so-called specificity of an antibody, defined as its propensity to bind to one protein, but not to others is difficult, if not impossible to test unambiguously by conventional methods. Accordingly, it remains uncertain whether an antibody is binding to the correct target. This potential lack of antibody specificity has huge economic and health implications.
How Emerge Biotech helps to solve this problem?
Emerge Biotech established a cost-effective and unequivocal approach to test the specificity of antibodies using a technology called RNA interference (RNAi) or gene silencing. RNAi is a conserved biological process by which messenger RNA (mRNA), the genetic information for the synthesis of a protein is specifically targeted and destroyed. This subsequently leads to the depletion of the corresponding protein. So how does this help to examine the specificity of antibodies? The answer is as simple as elegant. Antibodies raised against the depleted protein will cease to bind if they are specific. On the other hand, off-target effects of antibodies are apparent if antibody binding is not affected by the depletion of the target protein.
The genetic depletion of an antibody target therefore allows to test antibody specificity unambiguously and in a quantitative manner.