Man-made antibodies may change the future of drug development – here’s why
Sometimes an idea seems so logical and elegant at first glance, that you later wonder why no one thought of it before. Two researchers from LACDR have teamed up to develop a completely synthetic alternative to antibodies—one that mimics their size, shape and function, but which is cheaper, more stable, and faster to produce.
Can we make something that works like an antibody, but completely synthetic, a stable drug without serious side effects? That is what chemists Sebastian Pomplun and Matthias Barz wondered. After all, antibodies are complex, and therefore expensive to make. In addition, they are difficult to store and can sometimes cause immune reactions. This is exactly where Pomplun and Barz saw opportunities for improvement.
‘They’re like a flexible skeleton with strong sidechains—imagine a bottlebrush at the nanoscale.’
‘They’re like antibodies in disguise’
By combining their expertise in peptide synthesis (Pomplun) and polymer chemistry (Barz), they created particles that look and behave like real antibodies. They are the Y-shaped proteins used by our immune system and many modern therapies. ‘They’re like antibodies in disguise,’ Barz says, ‘but more stable and easier to produce.’ They don’t need to be stored at cool temperature, so patients can take the drug home and administer it themselves.
Unlike natural proteins, which can easily break down when heated or frozen, these synthetic versions maintain their size and shape. ‘That’s because they don’t fold into a 3D-structure like proteins,’ Pomplun explains. ‘They’re like a flexible skeleton with strong sidechains—imagine a bottlebrush at the nanoscale.’ This simple architecture is the secret to their stability: the molecules have only a ‘primary structure’, so they don’t unravel under stress, unlike real antibodies with their complex folds.
It worked from the very first experiment
So how do you get these antibody mimics to recognise targets like cancer cells? It’s all in the add-ons. ‘We can attach specific small peptide binders to interact with specific cells, just like natural antibodies,’ says Pomplun.
‘It’s exciting to see that our concept works.’
The researchers were stunned by how well the concept worked. ‘Quite unexpectedly, it worked from the very first experiment,’ Barz says. Such an elegant, revolutionary, and yet simple concept to create antibody-like molecules by chemical synthesis. Why has no one else executed this idea already? ‘We ask ourselves that too’, Barz laughs. ‘One explanation is that it requires very specific skills in both peptide and polymer chemistry. Not many people have that combination.’ Like many innovations, it looks simple with hindsight knowledge, but until you have done it, you obviously cannot predict whether it will work.
What does this discovery mean for patients?
Beyond the science, both researchers are motivated by what their discovery could mean for patients. Pomplun: ‘Antibodies are an amazing invention of evolution, but we can push them further with synthetic tools, using chemistry to mimic and improve on nature. It’s exciting to see that our concept works.’ The researchers really believe this can change how drugs are made and delivered. They still need to test how the molecules behave in living systems, but the outlook is promising. That belief has led them to start a spin-off company, aiming to bring their research from the lab to the real world.
Their story is a powerful reminder of what happens when the right minds (and molecules) come together. Barz concludes: ‘We both love doing beautiful chemistry that makes a difference. This is one of those rare projects where everything just falls into place.’