Tumor-specific polycistronic miRNA delivered by engineered exosomes for the treatment of glioblastoma

• DOI: 10.1093/neuonc/noad199
• Publication Date: 2023-10-17T20:10:40Z
• Authors: Malcolm F McDonald; Anwar Hossain; Eric N Momin; Irtiza Hasan; Sanjay Singh; Satoshi Adachi; Joy Gumin; Daniel Ledbetter; Jing Yang; Lihong Long; Marc Daou; Sricharan Gopakumar; Lynette M Phillips; Brittany Parker K...; Frederick F Lang
• Keywords: Exosome

Abstract Background Glioblastoma (GBM) has poor prognosis due to ineffective agents and delivery methods. MicroRNAs (miRs) have been explored as novel therapeutics for GBM, but the optimal miRs ideal strategy remain unresolved. In this study, we sought identify most effective pan-subtype anti-GBM develop an improved system these miRs. Methods We conducted unbiased screen of over 600 against 7 glioma stem cell (GSC) lines representing all GBM subtypes a set pan-subtype-specific then used available TCGA patient outcomes miR expression data hone in on that were likely be clinically effective. To enhance miRs, generated polycistronic plasmid encoding 3 (pPolymiR) HEK293T cells biofactories package pPolymiR into engineered exosomes (eExos) incorporate viral proteins (Gag/VSVg) their structure (eExos+pPolymiR) function. Results Our stepwise identified miR-124-2, miR-135a-2, let-7i across with clinical relevance. Delivery eExos+pPolymiR resulted high GSCs, significantly decreased GSC proliferation vitro. prolonged survival GSC-bearing mice vivo when compared eExos carrying each individually or cocktail. Conclusion eExos+pPolymiR, which includes anti-glioma-specific combination encoded exosome platform, represents new potentially powerful therapeutic.