Increasing the value proposition of the IOF programs CRISParray and Amalus: CRISPRi-based target deconvolution of fibroblast modulators

15 July 2023 → 14 February 2025
Regional and community funding: Industrial Research Fund
Research disciplines
  • Medical and health sciences
    • Cellular interactions and extracellular matrix
    • Transcription and translation
    • Cancer therapy
    • In vitro testing
    • Pharmacodynamics
target deconvolution cancer-associated fibroblast drug discovery CRISPRi mechanism of action
Project description

his application directly relates to two IOF programs: (i) Amalus, which develops unique small molecule therapeutics targeting fibroblasts, and (ii) CRISParray, which proposes a highly comprehensive CRISPRi screening for target deconvolution, a technology not available elsewhere.

VCs regard the Amalus program as highly valuable, but the trigger for VC investment in the Amalus program will be target deconvolution. At the same time, there is a very concrete market pull for technology demonstration of the CRISParray program in target deconvolution. This clearly represents a unique opportunity for synergism between two UGent valorization tracks.

The present proposal aims to kill these two birds with one stone by using the arrayed CRISPRi screening technology of CRISParray to deconvolute the molecular target of the fibroblast modulators developed by Amalus. In this way, the value proposition and investor-readiness of both programs will increase significantly:

►    It will provide a (currently lacking) proof of concept in target deconvolution for CRISParray.

►    Target identification will trigger VC investment in Amalus (as communicated by multiple VCs, see Annex 1).

Preliminary data supporting this proposal has been generated by combined forces of the involved laboratories, but further steps require dedicated financing, hence this application. We propose a workflow in which we will condict final validation of the cell models needed for the target deconvolution study, upon which we will perform this study on the Amalus compounds using the CRISParray technology. We will then validate the identified candidate targets in vitro, and will also benchmark the results of the CRISParray technology against a well-established external target deconvolution technique at a CRO.