Goals

Vision

The vision of the Center is to enable rational design of effective RNA drugs by increasing their potency and efficacy and by achieving maximal tolerability (i.e. minimization of unwanted adverse effects). To this end, we will map RNA accessibility over the entire transcriptome, characterize RNA drug effects on gene expression and use experimental data to design computational algorithms that can be used to predict effective and safe RNA therapeutics. These results will be of value to RNA drug development in the medium term (3-10 years) and will additionally provide insights into the RNA structure and the RNA-protein interactome in human cells and allow computational modeling of post-transcriptional gene regulation. To achieve these goals, COAT will gather expert experimentalists and computational biologists from world class academic groups and the Danish vanguard pharmaceutical SME Santaris Pharma in a cross-disciplinary collaboration. Experiments will be based on high-throughput technologies, such as next generation sequencing and microarrays. The results generated will represent an invaluable resource for the scientific community and help researchers both in academia and the industry to guide the design of novel RNA-targeted medicines for improvement of human health.

Objectives

The main objective of COAT is to facilitate the design of efficient and safe RNA drugs. The most direct means of translating genomic information into new drugs is by targeting RNAs that are associated with disease processes. The results produced by COAT aim at simplifying the route from the good idea to the development of an effective treatment. Currently, many of these ideas are not pursued, because specific drugs are very difficult and expensive to develop. By exploring and mapping the underlying principles of RNA drug design, we want to improve the process and success rate of designing RNA drugs targeted against any human gene. This will lower the practical and economical threshold for designing such drugs and make small biotech companies in Denmark and elsewhere able to generate RNA drugs to more diseases and pursue diseases with smaller patient populations.  Within 10-15 years, it is possible that the results from COAT will contribute to the development of cures and treatments for millions of humans. Moreover, additional objectives of COAT are to help Denmark maintain a leading role within RNA drug design by creating a world class research environment with a strong international network and to increase the understanding of how RNA structure and RNA-protein interactions affect gene expression.

Envisioned results

The main result of COAT will be an improvement of the ability to design safe and effective RNA drugs, making drug development more efficient and facilitating development of drugs for currently unmet medical needs. We will achieve this by developing the following:

  1. A transcriptome-wide map of regions accessible for RNA drugs.
  2. Computational methods for prediction of safer RNA drugs with fewer side effects.
  3. Computational methods for prediction of effective RNA drugs.

The research will also have important implications for more basic research and will be an important step forward in the functional annotation of the human genome by identifying RNA structure and Protein-RNA interactions, thereby leading to an increased understanding of post-transcriptional regulation and its implications for human disease. The data produced by COAT will be available for the scientific community (academic and commercial) through the UCSC genome browser interface.

Moreover, in Denmark, COAT will generate a world class academic environment with outstanding international collaborators dedicated to research in RNA drugs and post-transcriptional regulation. This will:

  1. Create the basis necessary for making new inventions related to the RNA drug field and convert these to new intellectual property.
  2. Improve and increase teaching in these subjects for the Molecular Biomedicine, Biochemisty, Bioinformatics, and Biology educations at University of Copenhagen.
  3. Train PhDs and postdocs in these topics.
  4. Increase collaboration with leading international scientists in the field and recruit outstanding researchers from abroad.

This environment will help Denmark and especially Santaris Pharma A/S maintain a leading position in the RNA drug field.