miRNA therapeutics in precision oncology: a natural premium to nurture

Abstract

The dynamic spectrum of microRNA (miRNA) has grown significantly over the years with its identification and exploration in cancer therapeutics and is currently identified as an important resource for innovative strategies due to its functional behavior for gene regulation and modulation of complex biological networks. The progression of cancer is the consequence of uncontrolled, nonsynchronous procedural faults in the biological system. Diversified and variable cellular response of cancerous cells has always raised challenges in effective cancer therapy. miRNAs, a class of non-coding RNAs (ncRNAs), are the natural genetic gift, responsible to preserve the homeostasis of cell to nurture. The unprecedented significance of endogenous miRNAs has exhibited promising therapeutic potential in cancer therapeutics. Currently, miRNA mimic miR-34, and an antimiR aimed against miR-122 has entered the clinical trials for cancer treatments. This review, highlights the recent breakthroughs, challenges, clinical trials, and advanced delivery vehicles in the administration of miRNA therapies for precision oncology.

Keywords: cancer; liposomes; miRBase; miRTarBase; microRNAs.

Figure 1.

A basic overview of miRNA biogenesis [15]. RNA POL II: RNA polymerase II; DGCR8: DGCR8 microprocessor complex subunit

Figure 2.

Tumor suppressive and Oncomeric miRNAs therapeutic as mimics and antimiRs. Part (A): depiction of some of the miRNA mimics as therapeutic agents targeting genes and various types of cancer. Part (B): illustration of a few of the miRNA antimiRs as therapeutic agents targeting the genes and different kinds of cancer. KRAS: KRAS proto-oncogene; BCL2: B-cell lymphoma 2

Figure 3.

The major stages in the production of miRNA therapeutics are described. The initial step for the preparation of miRNA therapeutic is the proper identification of candidates of miRNA by in vitro experiments. The generation of chemical manipulations and mechanisms of delivery for miRNA antimiRs and mimics for the in vivo modeling is the next significant challenge. Chemical changes, such as the insertion of a 2-O-methyl group or LNAs, can dramatically improve stability. A lipid nanoparticle, like NLEs, and a dendrimer complex containing target moieties are two typical delivery strategies. After clearing these challenges, short RNA therapy candidates must go through extensive disease-specific in vivo experiments in animal models. To minimize early clinical trial failures, a careful review of toxicity studies and target engagement is essential [12]