Team: Daniel Warmerdam, Rob Wolthuis & Ruud Wijdeven

CRISPR is a revolutionary gene editing technology to modify DNA effectively and with high precision. Already approved for the treatment of sickle cell disease, CRISPR therapies are expanding rapidly beyond the lab and progressing into curative therapies(1,2). Recent advances have made it possible to inject RNA-based CRISPR components directly into the bloodstream using lipid nanoparticles (LNPs)(3). Amsterdam UMC has been at the forefront of these developments, offering the first intravenous LNP-based CRISPR treatment for a hereditary disorder in 2024(4). Here, we will create a regulatory framework to start providing such therapies, in close contact with EMA(5) and the national competent regulatory agencies. Specifically, we will optimize and leverage recent technological advances towards novel CRISPR-mediated treatment options for two hereditary pediatric diseases that severely affect vision and brain function, aggressive primary and metastatic cancers that are nano-particle accessible (e.g. those residing in the lung and liver, and more difficult to penetrate tumors such as pancreatic cancer), and Alzheimer’s disease which is linked to a specific high-risk allele, APOE4, by gene editing of astrocytes. By designing safe and precise gene-editing and cancer genome-targeting tools, and building the necessary infrastructure for clinical trials, we are reaching for effective and tailor-made therapies for ADORE and Amsterdam UMC patients by the end of this project, and open new opportunities for others.

1. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
2. Is CRISPR safe? Genome editing gets its first FDA scrutiny
3. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis
4. CRISPR-Based Therapy for Hereditary Angioedema
5. Genome-editing medicinal products: the EMA perspective