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      Therapeutic advances of miRNAs: A preclinical and clinical update

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          Abstract

          miRNAs, a class of small endogenous RNAs, are one of the essential biopharmaceuticals which are in commercial spans as next-generation medicine in recent times. A snapshot of the current scenario regarding the miRNAs as biopharmaceuticals have been discussed. In this work, biopharmaceutical companies working with miRNAs and the current status of preclinical/clinical trials about miRNA therapeutics have been reviewed. Finally, recent updates on the absorption, distribution, metabolism, and excretion (ADME), as well as a delivery system of miRNAs, have been illustrated.

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          MicroRNAs: genomics, biogenesis, mechanism, and function.

          David Bartel (2004)
          MicroRNAs (miRNAs) are endogenous approximately 22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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            MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice.

            Angelika Bonauer, Guillaume Carmona, Masayoshi Iwasaki … (2009)
            MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Here, we show that the miR-17approximately92 cluster is highly expressed in human endothelial cells and that miR-92a, a component of this cluster, controls the growth of new blood vessels (angiogenesis). Forced overexpression of miR-92a in endothelial cells blocked angiogenesis in vitro and in vivo. In mouse models of limb ischemia and myocardial infarction, systemic administration of an antagomir designed to inhibit miR-92a led to enhanced blood vessel growth and functional recovery of damaged tissue. MiR-92a appears to target mRNAs corresponding to several proangiogenic proteins, including the integrin subunit alpha5. Thus, miR-92a may serve as a valuable therapeutic target in the setting of ischemic disease.
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              The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.

              Brenda Reinhart, Frank J Slack, Michael Basson … (2000)
              The C. elegans heterochronic gene pathway consists of a cascade of regulatory genes that are temporally controlled to specify the timing of developmental events. Mutations in heterochronic genes cause temporal transformations in cell fates in which stage-specific events are omitted or reiterated. Here we show that let-7 is a heterochronic switch gene. Loss of let-7 gene activity causes reiteration of larval cell fates during the adult stage, whereas increased let-7 gene dosage causes precocious expression of adult fates during larval stages. let-7 encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3' untranslated regions of the heterochronic genes lin-14, lin-28, lin-41, lin-42 and daf-12, indicating that expression of these genes may be directly controlled by let-7. A reporter gene bearing the lin-41 3' untranslated region is temporally regulated in a let-7-dependent manner. A second regulatory RNA, lin-4, negatively regulates lin-14 and lin-28 through RNA-RNA interactions with their 3' untranslated regions. We propose that the sequential stage-specific expression of the lin-4 and let-7 regulatory RNAs triggers transitions in the complement of heterochronic regulatory proteins to coordinate developmental timing.
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                Author and article information

                Contributors
                Chiranjib Chakraborty
                Sang-Soo Lee
                Journal
                Journal ID (nlm-ta): J Adv Res
                Journal ID (iso-abbrev): J Adv Res
                Title: Journal of Advanced Research
                Publisher: Elsevier
                ISSN (Print): 2090-1232
                ISSN (Electronic): 2090-1224
                Publication date PMC-release: 29 August 2020
                Publication date Collection: February 2021
                Publication date (Electronic): 29 August 2020
                Volume: 28
                Pages: 127-138
                Affiliations
                [a ]Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore Rd, Kolkata, West Bengal 700126, India
                [b ]Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Gangwon-Do 24252, Republic of Korea
                [c ]Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea
                Author notes
                [* ]Corresponding authors at: Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore Rd, Jagannathpur, Kolkata, West Bengal 700126, India (C. Chakraborty). Institute for Skeletal Aging & Orthopedic Surgery, Hallym University Hospital-College of Medicine, Chuncheon-si, Gangwon-do 200-704, Republic of Korea. (S.-S. Lee). drchiranjib@ 123456yahoo.com chiranjib.chakravartty@ 123456adamasuniversity.ac.in 123sslee@ 123456gmail.com totalhip@ 123456hallym.ac.kr
                [1]

                Both the authors contributed equally.

                Article
                Publisher Item ID: S2090-1232(20)30196-X
                DOI: 10.1016/j.jare.2020.08.012
                PMC ID: 7753224
                PubMed ID: 33364050
                SO-VID: e689cc8e-6ffc-42c9-9778-56cc845fe42a
                Copyright © © 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 29 January 2020
                Date revision received : 10 June 2020
                Date accepted : 17 August 2020
                Categories
                Subject: Article

                Keywords: mirna,next-generation medicine,biopharmaceuticals
                Data availability:
                Keywords: mirna, next-generation medicine, biopharmaceuticals

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