A Digital Approach to Novel RNA Antibiotics
for Health and Disease
Conventional antibiotics generally work against a broad spectrum of bacterial pathogens. This promotes the development of antibiotic resistance and damages our protective microbiota, which can have unwanted effects on our health. New antibiotics are therefore needed that can directly target individual pathogens, leaving beneficial bacteria unharmed.
In a multidisciplinary approach, our team is researching antibiotics based on RNA-like molecules, so-called peptide nucleic acids (PNA), which can be used to specifically attack individual bacterial strains. These RNA antibiotics can be modified through simple chemical means to achieve effectiveness against emerging pathogens.
In order to automate this process, we are creating a digital platform using high-throughput processes and machine learning, that will enable researchers to specifically design drug molecules against a variety of dangerous pathogens.
Peptide nucleic acids are RNA-like molecules that bind to messenger RNA through complementary base pairing and can inhibit the production of proteins. This approach has already been confirmed to be effective in preclinical studies, but there are many open questions, for instance about the rules for programming such RNA antibiotics, mechanisms of resistance development, and possible toxicity to host cells and non-targeted members of the microbiome. We are pursuing a combination of transcriptome analysis and machine learning to understand the effects of PNAs on bacterial pathogens and to identify effective PNA candidates.
The goal of our research is to establish effective PNA candidates for important clinical pathogens. Towards this purpose, we will characterize the molecular basis of PNA activity and resistance development through the systematic analysis of high-throughput data. The knowledge we gain from these studies will form the basis for future logic design of RNA antibiotics to use against multi-drug resistant pathogens and editing the microbiome.
The development of programmable antibiotics will have major implications for the treatment of infection: as only the particular strain targeted is affected, issues of resistance development in other bacteria can be avoided. Additionally, this approach will avoid harming our natural commensal bacteria. This strategy could also be used to target specific functions of bacteria, for instance so that resistant bacteria become sensitive to conventional antibiotics, or pathogens no longer express toxins. Since certain bacterial pathogens are also associated with tumorigenesis, RNA antibiotics could also be of interest for cancer treatment or prophylaxis in the future.
• Kristina Popova
• Jakob Jung
• Afsaneh Khani
Prof. Dr. Jörg Vogel
Dr. Franziska Faber
Prof. Dr. Lars Barquist