Protein missile raises possibility of disease breakthroughs

University of Dundee researchers have shown that it is possible to rapidly target and destroy specific proteins in cells, raising the possibility of developing new ways of targeting 'undruggable' proteins in diseases. 

Proteins, known as the building blocks of life, are vital to our existence and are found in every cell on Earth. They come in a huge variety of forms and perform a wide range of functions, including defending against diseases. In the vast majority of human diseases, amplification or genetic mutations alter the protein function in cells and this is what causes the damage that diseases wreak on the body.

It is thought that only a small percentage of proteins can be targeted for inhibition by conventional drugging approaches, while the rest of the proteins are termed undruggable. Being able to degrade these proteins inside the cells offers a unique opportunity for therapeutic intervention.

Now the Dundee team, led by Dr Gopal Sapkota from the University's School of Life Sciences, have engineered an Affinity-directed PROtein Missile (AdPROM) system that allows for the efficient and rapid degradation of specific target proteins in cells. The system uses small affinity probes, termed nanobodies or monobodies, which bind and recruit specific target proteins to the cellular protein degradation machinery.

"For the first time we have shown that it is possible to target endogenous proteins for complete degradation with AdPROM," said Dr Sapkota. "This is extremely exciting and has far-reaching applications and implications for both research and drug discovery.