Targeted Delivery of Microrna Sponge Short-Hairpin Rna Via Vir-Inspired Biotechnical Vector: Enhancing Cancer Therapy Publisher



H Rozbahani HANANEH ; A Zangooie ALIREZA ; Sm Mirabdolhosseini Seyed MOHSEN ; N Fatemi NAYERALSADAT ; M Norouzinia MOHSEN ; As Sadeghi Amir SAEED ; Z Salehi ZAHRA ; E Nazemalhosseinimojarad EHSAN
Source: Gene Expression The Journal of Liver Research Published:2025

Abstract

Targeted drug delivery remains a major challenge in cancer therapy, often limiting both efficacy and safety. Although microRNA sponges and short-hairpin RNAs show potential for gene-based cancer treatment, their clinical use is restricted by delivery inefficiency, off-target effects, cytotoxicity, and instability. Viral vectors offer high efficiency but are associated with issues such as immune responses, insertional mutagenesis, and limited cargo capacity. Non-viral carriers are safer and more affordable but suffer from poor transfection efficiency, instability, and inadequate endosomal escape. These limitations hinder the clinical application of RNA therapeutics. The Vir-inspired Biotechnical Vector (VIBV) is a novel hybrid platform that combines viral and non-viral elements with nanotechnology to enable personalized, tumor-specific gene therapy. Engineered with a spindle-shaped nanocore and a polyethylene glycolylated liposomal shell, VIBV ensures immune evasion, prolonged circulation, and controlled therapeutic release triggered by tumor microenvironmental cues such as acidity, hypoxia, and elevated glutathione levels. It delivers oncogenic microRNA sponges, short-hairpin RNAs, tumor-specific antigens, and cyclin-targeting RNAs to enhance gene silencing, immune activation, and tumor suppression. This review examines the limitations of current delivery systems and presents VIBV as a promising next-generation strategy with improved biocompatibility, targeting precision, and potential for cost-effective, personalized cancer therapy, while also addressing its remaining challenges and prospects. © 2025 Elsevier B.V., All rights reserved.