Vigyan Yuva awardee Vishal Rai: Chemical toolbox for precision therapy
The chemistry winner works on the engineering of proteins, assembling proteins or antibodies together with a cargo to make therapeutics more effective.
Vishal Rai of the Indian Institute of Science Education and Research Bhopal (IISERB), one of the winners of this year’s Vigyan Yuva Shanti Swarup Bhatnagar awards in Chemistry, works on the chemistry of engineering proteins for more effective therapeutics. He explains what it takes to build a chemical toolbox to ensure that proteins or antibodies assembled with a cargo together can perform the right functions at the right place.
What I do
Protein engineering is like making any other machine, and it requires the assembly of components to deliver the desired function. Proteins and antibodies must be assembled with other components for biotechnology and therapeutics. The proteins and the antibodies will have specific properties, but one would want to empower them with additional functions. Such technological demands require a precise chemical toolbox, which is what we develop. The resultant molecular machines are called protein bioconjugates or antibody bioconjugates.
With a randomly organised machine, we can never be sure of reproducing a performance, good or bad. The same is true for protein-based and antibody-based bioconjugates. That is why a toolbox capable of highly selective engineering is highly sought after by the biotechnology and biopharmaceutical industries.
How I do it
Although antibodies are very selective in differentiating tumour cells from normal cells, they are not great killers, so a higher antibody dose must be given to the patient. A better way is to take an antibody and then attach a small toxic molecule. Now, the antibody only has to target the tumour precisely, while the toxic molecule can kill it. Such a job distribution is more effective and reduces the dose required for the treatment.
Again, these toxic molecules have to be attached to the antibodies in a very selective manner so that they do not disturb their inherent property of specific tumour targeting. So, chemical technologies are needed to engineer these antibodies with high precision.
Around a decade ago, it was believed that such technologies were not possible and that one could not control these selectivities. Our first few years, in fact, were about establishing the principles and examining whether it is possible. Subsequently, this ground knowledge helped us develop the solutions.
Our chemical toolbox for the precision engineering of proteins meets multiple existing technological demands and paves the way for next-generation therapeutics. Our startup, Plabeltech, is working specifically on an antibody-drug conjugate (ADC) and an antibody-fluorophore conjugate (AFC) at present. For ADC, the antibody delivers the drug specifically to the tumour, and the latter is entrusted to kill it.
Similarly, the antibody can deliver a fluorophore that glows with NIR light so that surgeons can differentiate between the normal and tumour parts. In addition to serving our translational efforts, Plabeltech is using the toolbox to provide services to the biotech and biopharma sectors.