Upregulation

2025-2027

This project has two interconnected areas of work, which support each other to make the ASO development process faster and more reliable.

The team is looking at two primary candidate techniques for upregulation:

• CRISPR-Lock platform for precise RNA modulation (Rinaldi)
• Upstream open reading frame (uORF) disruption for controlled protein upregulation (Roberts)

This work will be informed by the ASO patent database model (helping us design our candidate molecules), and candidate molecules will be tested using the CellXpress.ai culture system.

By the end of this work, we hope to identify RNA elements whose modulation can upregulate protein levels by >25%.  

Based on the outputs of the screens, we hope to develop and test uORF-disrupting ASOs/sgRNAs, aiming to demonstrate protein-level upregulation of ≥50% for at least one target by the end of 2027.