LIPCAS (LIPid nanoparticle-mediated CRISPR/Cas9 delivery for anti-PD-L1 therapy in glioblastoma)

This project aims to harness lipid nanoparticle (LNP) technology to deliver anti-PD-L1 CRISPR/Cas9 systems directly to glioblastoma stem cells (GSCs), reactivating immune responses against this aggressive tumor type. Building on Dr. Shambhavi Pandey’s published work utilizing CRISPR/Cas9 delivery via VPX-CD133 nanocomplexes—targeting CD133-positive cancer stem cells and inducing up to 81% tumor volume reduction in vivo—this approach proposes to encode knockouts or modifications of PD-L1 in GSCs. The LNPs will be engineered with selective-organ-targeting (SORT) lipid formulations that enhance brain tropism, ensuring focused delivery across the blood–brain barrier to reach peritumoral and stem cell niches.

In parallel, the project will assess the immunoregulatory effects of reactivating immune surveillance in the GSC-enriched microenvironment, aiming to shift the tumor from immune-evasive to immunologically vulnerable. The feasibility will be established through in vitro assays and orthotopic GBM models, monitoring PD-L1 suppression, immune cell infiltration, and survival outcomes. The integrated strategy—combining Dr. Pandey’s expertise in nanoparticle-mediated CRISPR delivery with innovative SORT-LNP design—lays the groundwork for a next-generation, immune-restorative gene therapy targeting glioblastoma at its root. This research is funded by the 2023 Beatriu de Pinós (BP) program, within the call for postdoctoral researcher incorporation into the Catalan science and technology system (Ref 2023 BP 00202)