MiRNA inhibition in tissue engineering and regenerative medicine

Abstract

MicroRNA (miRNA) are noncoding RNA that provide an endogenous negative feedback mechanism for translation of messenger RNA (mRNA) into protein. Single miRNAs can regulate hundreds of mRNAs, enabling miRNAs to orchestrate robust biological responses by simultaneously impacting multiple gene networks. MiRNAs can act as master regulators of normal and pathological tissue development, homeostasis, and repair, which has recently motivated expanding efforts toward development of technologies for therapeutically modulating miRNA activity for regenerative medicine and tissue engineering applications. This review highlights the tools currently available for miRNA inhibition and their recent therapeutic applications for improving tissue repair.

Light-Triggered RNA Release and Induction of Hmsc Osteogenesis Via Photodegradable, Dual-Crosslinked Hydrogels

“…Delivering small interfering RNA (siRNA) or microRNA (miRNA) [17,18] to inhibit gene expression post-transcriptionally is a promising biomedical technology that has been investigated for many applications including cancer therapeutics [19][20][21][22][23], wound healing [24][25][26], and tissue regeneration [6][7][8][9][10][27][28][29][30][31][32]. For example, RNAs have been used in tissue regeneration to induce the differentiation of human MSCs (hMSCs) [6][7][8][9][10], canine MSCs [30] and rat MSCs [31] into osteoblasts [6][7][8][9]30,31], chondrocytes [10] or adipocytes [7,8].…”

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

“…In the line of miRNA inhibition therapy, three different strategies are available: antisense modified oligonucleotides (AMOs)-also known as anti-miRs or antagomiRs, miRNA masks or "blockmiRs"-miRNA sponges and small molecule inhibitors such as dihydropteridine ATP analogs and some diazobenzenes [25] (Figure 3b). AntagomiRs are the first type of miRNA inhibitors to demonstrate effectiveness in mammals; [26] they work by binding with high affinity to individual miRNAsdue to their chemical modifications-so that the interaction with the target mRNA is prevented.…”

“…The vast potential of miRNA therapies for tissue repair and RM has been extensively reviewed in the last few years in either general terms [25,141] or with more focused applications in mind such as bone/orthopedics, [104,142] angiogenesis, [143] the cardiovascular system, [144] or skin, [145] but the area of scaffold-based miRNA delivery in RM is still relatively in its infancy. To date, reports on scaffold-mediated miRNA delivery have focused more on specific areas of regenerative medicine including osteogenesis and bone repair as well as the cardiovascular arena (Table 2), but this progress report aims to give a broader overview encompassing a variety of areas of RM.…”

MicroRNAs: pleiotropic players in congenital heart disease and regeneration

“…Their modifications ensure high binding affinity to the targeted miRs and equip them with improved nuclease resistance (73). Next to the transient inhibition of miRs by AMOs, another class of stable miR inhibitors is raising interest: miR-sponges.…”

“…Mostly designed as single-stranded RNAs that generally exhibit a sequence that is fully complementary to the mature miR sequence, several chemically modified AMOs are available to improve their stability, binding affinity, and resistance to endonucleases. However, some AMOs, including those with modifications like methylation of nucleoside ribose 2'-hydroxyl groups ("OMe's"), inclusion of phosphorothiolate linkages (PS-modified OMe oligos), addition of N,N-dietyl-4-(4-nitronaphtalen-1-ylazo)-phenylamine ("ZEN"-modified OMe oligos), and 3-end substitution to cholesterol ("AntagomiRs")", have both advantages and disadvantages when used for miR inhibition (recently reviewed by Beavers et al) (73).…”