The Human Genome Project deciphered the DNA code that forms the basis for life. The effort also ushered in the age of “genomics,” with its astonishingly powerful tools for unraveling DNA and RNA. With genomics, researchers identified the genes that encode all processes in the human body and the basis of many diseases.
However, genomics fell short of delivering on the promise of new drugs to target all the newly discovered genetic causes of disease. In part, investigators have lacked tools to study the products of those genes: proteins.
Encoded by genes, proteins are the workhorses of the body. From photoreceptors in our eyes that allow us to see to digestive enzymes that break down the food we eat, proteins are at the heart of nearly all physiological processes. Understanding protein function is fundamental to understanding biology and human health.
Mutations in genes can alter how proteins work, leading to disease. Turning proteins "on" or "off" is the basis of drug development.
We need new technologies that can precisely target proteins and modify their function. These will “translate” the wealth of basic genomic knowledge into better understanding of human health and new therapeutics to fight disease.
Antibodies are specialized proteins that arise naturally from the body's immune system and protect us from harmful agents. The immune system generates an incredibly diverse array of unique antibodies, each with the capacity to specifically recognize a molecule foreign to the body, including proteins made by disease-causing organisms. Once an antibody binds to its molecular target, it recruits other components of the immune system to eliminate the threat.
Antibodies can be highly specific, allowing them to distinguish one protein from all others. They also recognize only one part of the surface of a protein, and thus can provide detailed information about protein structure and function.
For decades, researchers have exploited the natural ability of antibodies to target proteins. Antibodies can be created artificially and selected to block or activate a protein’s function to figure out what genes and proteins do in the body.
Meanwhile, drug developers recognized the power of antibodies to alter the function of target proteins and dreamt of using antibodies as 'magic bullets' to cure patients. Because of their specificity, antibodies almost never have off-target effects, unlike small molecule drugs. Today antibodies make up nearly half of all drugs on the market.
Despite their promise, the generation of useful antibodies for research or drug development still faces major hurdles.
Traditionally, antibodies are produced by injecting mice with a specific human target protein. The immune system is tuned to hone in on proteins that are different, but many mouse and human proteins are nearly identical, especially in the parts that perform the protein's function. Thus, the mouse immune system often cannot recognize the human protein as being different and fails to generate antibodies.
In addition, many of the protein targets needed to make antibodies are still extremely difficult to produce and require developing expertise in protein science.
More troubling, irreproducibility is now plaguing modern science and eroding public trust. Unreliable antibodies are often the cause. Many antibodies used in research are not properly validated, making it difficult for scientists to reproduce the results of pivotal antibody-based studies.