Therapeutic Potential of NF-κB Inhibition in Glioblastoma: Gene Therapy Approach with rAAV-5 Mediated IκBαM Overexpression.

Current treatment strategies for glioblastoma, including resection followed by concurrent chemotherapy/radiotherapy are not curative. Angiogenesis and hypoxia are two major factors responsible for GBM growth and resistance to existing therapies, leading to poor clinical outcomes. The transcription factor NF-κB induces tumour progression by activating genes associated with cell proliferation and angiogenesis. It is expressed constitutively in gliomas and is known to regulate the expression of HIF-1α and VEGF in GBM. As a result, NF-κB can be a potent target that can inhibit tumour growth/invasiveness by reducing hypoxia and angiogenesis, as well as preventing macrophage and microglia infiltration and generating inflammatory cytokines that cause gliomagenesis. AAV vectors are the typical transducing agents for gene therapy because they can infect a broad range of dividing and non-dividing cell types. AAVs have emerged as one of the most widely used methods for delivering genes into the central nervous system because of their broad range of infectivity, ability to induce long-term transgenic expression, and lack of toxicity. The present study aims to inhibit NF-κB activity by blocking its nuclear translocation via overexpression of IκBα utilising recombinant adeno-associated virus-5 plasmid as a gene therapy vector.