ncRNAs in Therapeutics: Challenges and Limitations in Nucleic Acid-Based Drug Delivery

Abstract

Non-coding RNAs (ncRNAs) are emerging therapeutic tools but there are barriers to their translation to clinical practice. Key issues concern the specificity of the targets, the delivery of the molecules, and their stability, while avoiding “on-target” and “off-target” side effects. In this “ncRNA in therapeutics” issue, we collect several studies of the differential expression of ncRNAs in cardiovascular diseases, bone metabolism-related disorders, neurology, and oncology, and their potential to be used as biomarkers or therapeutic targets. Moreover, we review recent advances in the use of antisense ncRNAs in targeted therapies with a particular emphasis on their basic biological mechanisms, their translational potential, and future trends.

The role of miRNA and lncRNA in heterotopic ossification pathogenesis

“…Therefore, constructs, such as locked nucleic acid [ 209 ], cholesterol-conjugated miRNA, lipid particles [ 210 ], or bacterially derived minicells, could be used [ 211 ]. Another issue is the stability of ncRNA, which could be improved by chemical modifications that prevent it from nuclease [ 208 , 212 ]. To avoid the immune response, chemical modifications or small molecule inhibitors of ncRNA could be used [ 163 ].…”

The Molecular Roles and Clinical Implications of Non-Coding RNAs in Gastric Cancer

“…Strategies including antisense oligonucleotide (ASO), RNA interference (RNAi) and CRISPR/Cas9 have been proposed to up-regulate the tumor inhibition of ncRNA using gene silencing techniques ( Chen et al, 2021b ). However, barriers to the translation of nucleic acid-based therapeutics into the clinic are related to their stability, specificity, delivery, and toxicity issues, such as “on-target” and “off-target” side effects ( Hueso et al, 2021 ). It is very important to conduct further in vitro and in vivo studies and clinical studies on the efficacy and safety of ncRNA to achieve precision medicine.…”

Epigenetic Regulation in Exposome-Induced Tumorigenesis: Emerging Roles of ncRNAs

“…Besides their potential application as antitumor drugs [174], they can be used as carriers to deliver proteins, vaccine antigens, and drugs to a specific site of action [175]. A particular application in the context of ncRNA-based therapy (discussed in Section 5.10) is that nanoparticles have been developed for the safe transference of nuclei acids and increasing their stability to reach their targets [176,177]. Moreover, the application of NMs for the improvement of the environment is promising for the reduction in contaminants.…”