TARGETING GLIOBLASTOMA STEM-LIKE CELLS USING BLOOD-BRAIN BARRIER-PENETRATING NANOCARRIER-DELIVERED CRISPR/CAS9- ENGINEERED THERAPEUTICS: A NOVEL APPROACH FOR PRECISION MEDICINE IN BRAIN TUMOR TREATMENT

Glioblastoma multiforme (GBM) is the most severe form of brain cancer partially due to GSC involvement in induction of brain cancer cells, proliferation of cancer cells and facilitate their dissemination around the whole body as well as for coming back of cancer cells. Due to the blood brain barrier (BBB), brain tumor medication access is a major challenge. The research takes an innovative look at using blood brain barrier permeating lipid nanoparticles (LNPs) to deliver the CRISPR/Cas9 gene editing system to GSCs. In another study, the ligation of a CRISPR-Cas9 system targeted at EGFR, PDGFRA and IDH1 oncogenes to LNP’s enabled the encapsulation properties for GSC targeted delivery. We achieved high rates of gene edit success while success of gene delivery was verified in laboratory tests accompanied with major decreases in GSC population growth and decreased movement, survival rates. The positive results observed in the research using orthotopic GBM mouse models induced substantial tumor inhibition as well as extended survival. Under the lens of histology, the increased cell death along with reduced expression of GSC markers was detected in treated tumors. Because CRISPR/Cas9-LNPs did not produce many adverse events in the body, they were excellent tolerators. Our results demonstrate the feasibility of treating GBM with the use of nanocarrier and CRISPR/Cas9 gene editing combined approach that effectively addresses BBB penetration barrier and the GSC resistance.