RNA-targeting small molecules


Proteins are large complex molecules that control many processes in the body. As enzymes, for example, they speed up the metabolism in our bodies and let us lead healthy lives. At the same time, hundreds of human proteins are known to cause disease. Due to structural challenges and a lack of certain features, and despite decades of medical progress, up to 90% of human proteins have been considered inaccessible to drugs, or simply ‘undruggable’.

However, due to recent leaps in research and development of new technologies, the notion of undruggability is being eroded. One such example are molecules that address diseases before the disease-causing proteins are synthesized, at the level of RNA.


In this blog, Dr. Nicole Biber, Head of Novel Modalities II at Bayer Pharmaceuticals, and Dr. Razvan Nutiu, Head of Life Science Technology at Bayer Pharmaceuticals, discuss how RNA-targeting small molecules could allow us to reach into the undruggable space and create new kinds of treatments for patients.

The potential of RNA-targeting small molecules

Nicole Biber: Traditionally, scientists have looked for pockets on the surface of disease-causing proteins that can bind drugs. Many small molecule drugs that we know today are built on the requirement that there are deep, clearly defined pockets on the surface of the protein. But if the pockets are too shallow or are missing altogether, it gets more difficult to develop drug molecules. So we need to look for different ways of addressing proteins.


One exciting new way of doing this is to target coding RNA, so RNA that encodes proteins. This could allow us to prevent disease-causing proteins from being built in the first place.


Razvan Nutiu: We could also enhance the synthesis of certain proteins that are desirable in fighting disease. Or we could target RNA that does not translate into proteins, so-called non-coding RNA, but can still cause cancer, cardiovascular, neurodegenerative and other disorders.


We have started to think more and more about the RNA-biology behind proteins. RNA-targeting small molecules could allow us to tackle diseases that we could not address before. What used to be undruggable is now just becoming ‘hard-to-drug’ and could one day, hopefully soon, be a new standard of care.

Razvan Nutiu
What used to be undruggable is now just becoming ‘hard-to-drug’ and could one day, hopefully soon, be a new standard of care.
Dr. Razvan Nutiu
Head of Life Science Technology at Bayer Pharmaceuticals

Use cases

Nicole Biber: Targeting RNA may be a promising approach in many disease areas where accessing the disease-causing protein is proving to be difficult. In recent years, the scientific community has learned a great deal about the process by which genetic information is converted into proteins, which in turn has led to the emergence of RNA-targeting small molecules. We are excited about this technology because it may allow us to intervene in a disease pathway earlier and more precisely. The beauty is that RNA-targeting small molecules are becoming one of many tools in our toolbox, giving us more options to address diseases.

Nicole Biber
The beauty is that RNA-targeting small molecules are becoming one of many tools in our toolbox, giving us more options to address diseases.
Dr. Nicole Biber
Head of Novel Modalities II at Bayer Pharmaceuticals

Razvan Nutiu: From a disease perspective, our work is indication-agnostic, meaning we do research across a broad range of therapeutic areas including cancer and inflammatory disease. Our goal is to develop new therapies that are not just incremental improvement but can really transform patients’ lives.


In some indications we do not yet know if going after a piece of RNA would be the way to go, but we have the opportunity to look at this as one option. The biology of RNA is so complex and rich that, despite increased knowledge of the role played by RNA in the progressions of disease, we have only scratched the surface. As we build a better understanding of the chemistry and biology of RNA, we will uncover more use cases and opportunities.

Where we stand today

Razvan Nutiu: One thing we are doing is to apply state-of-the-art RNA sequencing methods to unravel and better understand the complex biology of RNA. Our endeavor is to build up a comprehensive knowledge base that will serve as a go-to resource we can draw on as we develop new drugs. This will also help us identify previously undiscovered disease targets. My team, which has deep expertise across chemistry, biology and data science, aims to catalyze this process.


Nicole Biber: Bayer is traditionally strong in developing small molecules, and we want to bring those capabilities to the RNA-space. One way we are doing this is by looking into the depths of our existing vast compound library to identify compounds, which address the splicing of RNA. RNA-splicing is an important step as DNA is translated to build a protein, without which the correct protein cannot be formed. We are currently working on several projects in an early drug discovery stage.

Stepping into the future

Nicole Biber: One of the key next steps will be to create reliable evidence that RNA-targeting small molecules are effective, before they advance to preclinical and clinical research. It will take time to deliver this proof, but I am convinced that we are going to get there. Our teams have the know-how, the right type of energy and spirit.


Razvan Nutiu: I suppose it’s this spirit that attracted me to Bayer in 2021. The technologies we work on are new and we cannot predict their full potential yet, but the team is ready to give it its best shot. We will know when we see these molecules in the clinic. Data talks, after all. Personally, I am confident about the future of RNA-targeting small molecules. My overarching goal is that in a couple of years people will see these new technologies effectively address various diseases and say it’s possible because Bayer did it.