Customized Surface-Engineered “Nanoglue”: Unlocking Ultrasound-Triggered targeted delivery of CRISPR/Cas complex for Glioblastoma

Glioblastoma multiforme (GBM), constituting 50.1% of CNS tumors, is the most frequent malignant brain cancer with a median survival of 14.6 months, highlighting the urgent need for more effective treatment strategies. The rise of effective gene therapies especially CRISPR/Cas (“clustered regularly interspaced short palindromic repeats/associated protein 9”) based gene editing technology has sparked optimism for treating GBM. Given the ongoing challenges with CRISPR-Cas gene therapy, such as effective delivery across the blood-brain barrier (BBB), off-target effects, and immune responses associated with Cas9, this research proposal (CRISPRGlue) aims to develop ""nanoglues,"" a novel class of engineered nanogels for targeted delivery of CRISPR tools followed by ultrasound triggered release to address GBM treatment challenges at a European level. The gene editing efficacy of the CRISPR/Cas tools delivered by “nanoglues” will be preliminary investigated as a “proof of concept” by knock-down approach with GFP expressed U87MG cell line followed by targeting EGFR genes which are highly overexpressed in GBM sites. The project unites a dynamic researcher, Dr. Soumen Ghosh, with expertise in synthetic organic chemistry and protein science, alongside POLYMAT, an innovative institute focused on biomedical solutions utilizing nanogels for the controlled release of the CRISPR/Cas9 complex. Prof. Marcelo Calderón, the host supervisor, is a globally recognized researcher leading the “Responsive Polymer Therapeutics Group (RPTG),” a top team specializing in drug delivery using nanogels (NGs). The multidisciplinary expertise required for CRISPRGlue will be complemented by the Smart Bio-Interfaces group led by Prof. Gianni Ciofani. CRISPRGlue will advance the researcher’s career in both academic and non-academic fields by developing non-viral gene delivery systems to facilitate curative gene editing, empowering him to drive the translation of laboratory findings to pre-clinical trials.""