Combining CRISPR and AAV to selectively target oncogene-driven pediatric brain tumors
Drs. Marc Zuckermann and Lena Kutscher are working together with Drs. Stefan Pfister and David Jones to establish a new system for targeting oncogenic mutations in pediatric brain tumors at the Hopp Children’s Cancer Center (KiTZ) and the German Cancer Research Center (DKFZ) in Heidelberg, Germany. Our project’s objective is to combine tumor-specific CRISPR genome editing with tumor cell specific viral delivery.
This strategy applies to non-“druggable” oncogenes and should be unsusceptible to many known resistance mechanisms. As an initial proof-of-concept, we are focusing on BRAF(V600E)-driven pleomorphic xanthoastrocytoma (PXA) and H3.3(K27M)-driven diffuse intrinsic pontine glioma (DIPG) tumors. Both of these tumor types presumably rely on the mutated oncogene for survival. By combining tumor cell specific viral variants with oncogene-specific CRISPR molecules, we aim to establish a sufficiently precise gene therapy to treat patients with a therapeutically-relevant and safe viral dose. We will evaluate this approach for its treatment potential in a preclinical in vivo setting compared with standard-of-care therapy.