Therapeutic Applications of Poly-miRNAs and miRNA Sponges

Abstract

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play crucial roles in regulating gene expression, and their dysregulation is implicated in various human diseases. Over the years, several research groups have identified miRNAs as promising therapeutic targets for intervention. Therapeutic strategies involve either overexpression or knockdown of specific miRNAs. This review aims to provide a comprehensive overview of synthetic poly-miRNAs and miRNA sponges, highlighting their therapeutic applications. It begins with an introduction to miRNAs and their role in human diseases, followed by a detailed discussion on synthetic poly-miRNAs and miRNA sponges by exploring their application in cardiovascular, inflammatory, autoimmune, and metabolic disorders, as well as in cancer therapy. Additionally, strategies for targeted delivery, challenges, and limitations of these therapies are addressed.

Keywords: RNA-based therapy; biomedicine; miRNA; miRNA sponge; poly-miRNA.

Figure 1

Schematic representation of poly-miRNA genetic constructs and their mode of action. The figure illustrates how poly-miRNA genes can be arranged within a genetic vector, driven by either a polymerase II or III promoter. On the left, an example of a homo poly-miRNA is shown, where identical miRNA sequences are repeated. On the right, a hetero poly-miRNA is depicted, where different miRNA sequences (represented in various colors) are arranged within the construct. After transcription, the poly-miRNA adopts a typical pri-miRNA stem-loop structure, with each stem-loop separated by a ‘spacer sequence’ (yellow). The pri-miRNA is then processed into mature miRNAs, which assemble with the RISC and bind to the 3′ UTR of target mRNAs, leading to mRNA decay. Created in BioRender. Portugal, (2025) https://BioRender.com/rnbsn8z.

Figure 2

Schematic representation of synthetic miRNA sponges’ genetic constructs and their mechanism of action. The figure illustrates how miRNA sponge genes can be arranged within a genetic vector. On the left, an example of a homo sponge is shown, where identical MBSs are repeated. On the right, a hetero sponge is shown, where different MBSs (represented in various colors) are arranged within the construct; in both cases, the MBSs are separated by a spacer sequence (yellow). Once transcribed, the miRNA–sponge complex forms through complementary binding to the seed sequence of the miRNA, leading to the expression of target mRNA. Created in BioRender. Portugal, (2025) https://BioRender.com/79wvrsy.