The Challenges and Opportunities in the Development of MicroRNA Therapeutics: A Multidisciplinary Viewpoint

Abstract

microRNAs (miRs) are emerging as attractive therapeutic targets because of their small size, specific targetability, and critical role in disease pathogenesis. However, <20 miR targeting molecules have entered clinical trials, and none progressed to phase III. The difficulties in miR target identification, the moderate efficacy of miR inhibitors, cell type-specific delivery, and adverse outcomes have impeded the development of miR therapeutics. These hurdles are rooted in the functional complexity of miR’s role in disease and sequence complementarity-dependent/-independent effects in nontarget tissues. The advances in understanding miR’s role in disease, the development of efficient miR inhibitors, and innovative delivery approaches have helped resolve some of these hurdles. In this review, we provide a multidisciplinary viewpoint on the challenges and opportunities in the development of miR therapeutics.

The MicroRNA-Based Strategies to Combat Cancer Chemoresistance via Regulating Autophagy

“…Recently, the delivery approaches for miRNAs including viral vector-, lipid-, inorganic material-, polymer-, cell-, and 3D scaffold-based approaches have emerged ( 219 ). The lipid-based delivery systems such as liposomes, lipid nanoparticles, and solid lipid nanoparticles (SLNs) have been widely used for introduction of miRNAs.…”

“…Currently, the safety concerns of miRNA therapy including off-target side-effects, toxicity, and carcinogenicity have become big challenges. Nowadays, less than 20 miR targeting molecules have entered clinical trials, and none progressed to phase III ( 219 ). Hence, further research is needed to promote the application value of miRNA therapy.…”

miRNAs in Cardiac Myxoma: New Pathologic Findings for Potential Therapeutic Opportunities

“…The efficacy of drugs must be titrated against their off-target effects, such as negative impacts on the complement system, toxicity related to the vector, or interference with innate immunity [ 2 , 26 , 27 ]. Although some antago-miRs have been used in clinical trials against the hepatitis C virus and in other conditions [ 28 , 29 , 30 ], no study has investigated their role in cardiac tumors. However, targeted therapy to miRNA is known to be not free from side effects.…”

The Enticing Path of miR Therapeutics: Difficult but Not without Prospects

“…A lower number of miR therapeutics in the pipeline suggests an unexplainable hurdle in developing miR therapeutics [15]. In this issue, Momin et al summarized the challenges and opportunities in developing miR therapeutics from a multidisciplinary view [16]. In conclusion, the journey to developing miR therapeutics and identifying it as a biomarker is attractive but full of hurdles because of its ubiquitous expression, non-specificity, and delivery challenges.…”