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Byline: Nikita. Das, M. Manju, Premanand. Chandran, Mrunali. Dhavalikar, Padmavathi. Sivakumar, Menaka. Vimalanathan, Ganesh. Venkataraman Purpose: This study was conducted to assess the outcomes of bleb needling for the treatment [...]

MicroRNAs (miRNAs) mediate cell phenotype and tumor progression across various tissue types, acting via post-transcriptional repression of gene expression. Pre-clinical evidence highlights their therapeutic potential, but several challenges presently limit their clinical application in neuro-oncology. This review summarizes the evidence supporting miRNAs as biomarkers of cancer across tissue types, their potential role in cancer therapeutics, translational successes and failures of miRNA therapeutics, and how miRNA therapeutics may be adapted for applications in neuro-oncology. We highlight how the inherent complexity of miRNA regulatory networks poses difficulty in pinpointing specific targets while avoiding off-target effects, further compounded by drug delivery obstacles, including molecule stability and the blood-brain barrier, limiting therapeutic efficacy in neurologic indications. Combinatorial approaches with multiple miRNA types may enhance the efficacy and specificity of miRNA therapy. Overcoming drug delivery challenges in developing miRNA-based therapies for brain malignancies necessitates sophisticated delivery mechanisms, including bio-specific antibodies, intrathecal delivery, and nanoparticle and exosome-mediated transport. This review endorses the biological rationale for use of exogenous miRNAs as therapeutic agents in cancer, examining how challenges specific to neurotherapeutics, including delivery across the blood-brain barrier, might be overcome to potentially open the door to a novel class of agents in neuro-oncology.