Top Sector Life Sciences & Health (LSH) entails a broad scope of disciplines, from pharmaceuticals to medical technology and from healthcare infrastructure to vaccination. To realise its mission – vital citizens in a healthy economy - the Top Sector builds on the strengths of the Dutch LSH sector to address the biggest societal challenges in prevention, cure and care. By funding multidisciplinary public-private partnerships (PPPs) the Top Sector aims to facilitate innovation. Here we give an overview of  a number of funded R&D projects by Top Sector LSH. The page is updated continuously.

CRISPR-Cas9: from a molecular scissor to a surgical knife

Improving the CRISPR-Cas9 genome editing tool

In collaboration Biolegio, Erasmus MC aims to develop a DNA repair tool in which the molecular scissor (Cas9), a protein that is used to cut DNA, is irreversible bound to its CRISPR, a guide that allows Cas9 to find and repair, i.e., disease causing mutation. Their combined effort will allow them to transform the molecular scissor Cas9 in a surgical knife. Recent work at the Erasmus MC revealed that when Cas9 is unguided, severe DNA damage is introduced in the human cell. This finding lead to the idea that by locking the CRISPR in Cas9 the DNA damage can be prevented during the repair of disease causing mutations.

Within this project, the partners investigate the possibility to irreversibly bind the CRISPR in Cas9, by UV-crosslinking or chemical modifications. The CRISPR-Cas9 genome editing technology is widely used for research purposes and explored for clinical applications, but the ability of Cas9 to induce DNA damage was relatively unknown. Therefore no techniques are available at the moment to circumvent this problem.

This project will result in solid data, for the technical aspect, namely the irreversible binding of the CRISPR to Cas9. When successful, the method provides the foundation to reveal whether the CRISPR-Cas9 DNA repair technology can be brought a step closer to the clinic by analysing the safety requirements that are needed according to the European Medicines Agency.