Login Register Cart 0
Generic placeholder image

Current Biotechnology

Editor-in-Chief

ISSN (Print): 2211-5501
ISSN (Online): 2211-551X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

RNA-based Therapeutics: Master Regulator for Bioengineering Systems in Medicine World

Author(s): Malika Arora, Parveen Bansal and Richu Singla*

Volume 12, Issue 2, 2023

Published on: 05 May, 2023

Page: [67 - 78] Pages: 12

DOI: 10.2174/2211550112666230417100541

Price: $65

conference banner
Abstract

Ribonucleic acid (RNA) and its types have emerged as master regulators of biological processes and expanded knowledge regarding the role of RNA in the gene expression inside the cell have dramatically changed the therapeutic strategies in the past few years. RNA has become a focus for developing novel therapeutic schemes and hence RNA-based therapies, particularly in viral diseases have become more enthralling and promising. It is due to the fact that RNA offers various advantages in disease management as it can be edited and customized in its various forms such as secondary and tertiary structures. Principles and mechanisms regarding RNA therapeutics are well described in volumes, however, the information regarding long-awaited RNA-based drug development and potential hurdles as well as barriers in the way is still scattered. In this regard, these agents are required to overcome a plethora of barriers such as stability of drug targets, immunogenicity, adequate binding, targeted delivery, etc. to become effective drugs. Most of the trials are changing their way from in-vitro to in-vivo studies and it is not far away when RNA-based therapeutics will find their way from bench to bedside. In this communication, the authors give a brief review of important recent advances in above said domains of miRNA therapeutics.

Keywords: RNA, RNA therapeutics, disease management, biological process, mRNA, drug development.

« Previous Next »
Graphical Abstract

[1]
Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001; 409(6822): 860-921.
[http://dx.doi.org/10.1038/35057062] [PMID: 11237011]
[2]
Wan G, Liu Y, Han C, Zhang X, Lu X. Noncoding RNAs in DNA repair and genome integrity. Antioxid Redox Signal 2014; 20(4): 655-77.
[http://dx.doi.org/10.1089/ars.2013.5514] [PMID: 23879367]
[3]
Lekka E, Hall J. Noncoding RNA s in disease. FEBS Lett 2018; 592(17): 2884-900.
[http://dx.doi.org/10.1002/1873-3468.13182] [PMID: 29972883]
[4]
Kaczmarek JC, Kowalski PS, Anderson DG. Advances in the delivery of RNA therapeutics: from concept to clinical reality. Genome Med 2017; 9(1): 60.
[http://dx.doi.org/10.1186/s13073-017-0450-0] [PMID: 28655327]
[5]
Smith CIE, Blomberg P. [Gene therapy - from idea to reality]. Lakartidningen 2017; 114: 114.
[PMID: 29297925]
[6]
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet 2009; 10(3): 155-9.
[http://dx.doi.org/10.1038/nrg2521] [PMID: 19188922]
[7]
Moss KH, Popova P, Hadrup SR, Astakhova K, Taskova M. Lipid nanoparticles for delivery of therapeutic RNA oligonucleotides. Mol Pharm 2019; 16(6): 2265-77.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b01290] [PMID: 31063396]
[8]
Bekris LM, Leverenz JB. The biomarker and therapeutic potential of miRNA in Alzheimer’s disease. Neurodegener Dis Manag 2015; 5(1): 61-74.
[http://dx.doi.org/10.2217/nmt.14.52] [PMID: 25711455]
[9]
Reddy LV, Miller TM. RNA-targeted Therapeutics for ALS. Neurotherapeutics 2015; 12(2): 424-7.
[http://dx.doi.org/10.1007/s13311-015-0344-z] [PMID: 25753730]
[10]
De Majo F, De Windt LJ. RNA therapeutics for heart disease. Biochem Pharmacol 2018; 155: 468-78.
[http://dx.doi.org/10.1016/j.bcp.2018.07.037] [PMID: 30059676]
[11]
Lei B, Tian Z, Fan W, Ni B. Circular RNA: a novel biomarker and therapeutic target for human cancers. Int J Med Sci 2019; 16(2): 292-301.
[http://dx.doi.org/10.7150/ijms.28047] [PMID: 30745810]
[12]
Bansal P, Kumar A, Chandna S, Arora M, Bansal R. Targeting miRNA for therapeutics using a Micronome based method for identification of miRNA-mRNA pairs and validation of key regulator miRNA. miRNA Biogenesis. Springer 2018; p. 185-95.
[13]
Feng R, Patil S, Zhao X, Miao Z, Qian A. RNA Therapeutics - Research and Clinical Advancements. Front Mol Biosci 2021; 8: 710738.
[http://dx.doi.org/10.3389/fmolb.2021.710738] [PMID: 34631795]
[14]
Burnett JC, Rossi JJ. RNA-based therapeutics: current progress and future prospects. Chem Biol 2012; 19(1): 60-71.
[http://dx.doi.org/10.1016/j.chembiol.2011.12.008] [PMID: 22284355]
[15]
Lares MR, Rossi JJ, Ouellet DL. RNAi and small interfering RNAs in human disease therapeutic applications. Trends Biotechnol 2010; 28(11): 570-9.
[http://dx.doi.org/10.1016/j.tibtech.2010.07.009] [PMID: 20833440]
[16]
Spadaro S, Park M, Turrini C, et al. Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine. J Inflamm (Lond) 2019; 16(1): 1-1.
[http://dx.doi.org/10.1186/s12950-018-0202-y] [PMID: 30675131]
[17]
Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383(27): 2603-15.
[http://dx.doi.org/10.1056/NEJMoa2034577] [PMID: 33301246]
[18]
Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021; 384(5): 403-16.
[http://dx.doi.org/10.1056/NEJMoa2035389] [PMID: 33378609]
[19]
Karikó K. In vitro-transcribed mRNA therapeutics: out of the shadows and into the spotlight. Mol Ther 2019; 27(4): 691-2.
[http://dx.doi.org/10.1016/j.ymthe.2019.03.009] [PMID: 30905578]
[20]
Wittrup A, Lieberman J. Knocking down disease: a progress report on siRNA therapeutics. Nat Rev Genet 2015; 16(9): 543-52.
[http://dx.doi.org/10.1038/nrg3978] [PMID: 26281785]
[21]
Zhu Z, Zhang L, Sheng R, Chen J. Microfluidic-based cationic cholesterol lipid siRNA delivery nanosystem: Highly efficient in vitro gene silencing and the intracellular behaviour. Int J Mol Sci 2022; 23(7): 3999.
[http://dx.doi.org/10.3390/ijms23073999] [PMID: 35409359]
[22]
Jackson AL, Linsley PS. Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nat Rev Drug Discov 2010; 9(1): 57-67.
[http://dx.doi.org/10.1038/nrd3010] [PMID: 20043028]
[23]
Chakraborty C, Sharma AR, Sharma G, Doss CGP, Lee SS. Therapeutic miRNA and siRNA: moving from bench to clinic as next generation medicine. Mol Ther Nucleic Acids 2017; 8: 132-43.
[http://dx.doi.org/10.1016/j.omtn.2017.06.005] [PMID: 28918016]
[24]
Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 2013; 12(11): 847-65.
[http://dx.doi.org/10.1038/nrd4140] [PMID: 24172333]
[25]
Diener C, Keller A, Meese E. Emerging concepts of miRNA therapeutics: from cells to clinic. Trends Genet 2022; 38(6): 613-26.
[http://dx.doi.org/10.1016/j.tig.2022.02.006] [PMID: 35303998]
[26]
Sacco A, Martelli F, Pal A, et al. Regulatory miRNAs in cardiovascular and alzheimer’s disease: A focus on copper. Int J Mol Sci 2022; 23(6): 3327.
[http://dx.doi.org/10.3390/ijms23063327] [PMID: 35328747]
[27]
Taganov KD, Boldin MP, Baltimore D. MicroRNAs and immunity: tiny players in a big field. Immunity 2007; 26(2): 133-7.
[http://dx.doi.org/10.1016/j.immuni.2007.02.005] [PMID: 17307699]
[28]
Small EM, Frost RJA, Olson EN. MicroRNAs add a new dimension to cardiovascular disease. Circulation 2010; 121(8): 1022-32.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.889048] [PMID: 20194875]
[29]
Bhavya Pathak E, Mishra R. Deciphering the link between Diabetes mellitus and SARS-CoV-2 infection through differential targeting of microRNAs in the human pancreas. J Endocrinol Invest 2021; 45(3): 537-50.
[http://dx.doi.org/10.1007/s40618-021-01693-3] [PMID: 34669152]
[30]
Chakraborty C, Sharma AR, Sharma G, Lee SS. Therapeutic advances of miRNAs: A preclinical and clinical update. J Adv Res 2021; 28: 127-38.
[http://dx.doi.org/10.1016/j.jare.2020.08.012] [PMID: 33364050]
[31]
Hanna J, Hossain GS, Kocerha J. The potential for microRNA therapeutics and clinical research. Front Genet 2019; 10: 478.
[http://dx.doi.org/10.3389/fgene.2019.00478] [PMID: 31156715]
[32]
Benhamed M, Herbig U, Ye T, Dejean A, Bischof O. Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells. Nat Cell Biol 2012; 14(3): 266-75.
[http://dx.doi.org/10.1038/ncb2443] [PMID: 22366686]
[33]
He W, Xu J, Huang Z, Zhang J, Dong L. MiRNAs in cancer therapy: focusing on their bi-directional roles. ExRNA 2019; 1(1): 7.
[http://dx.doi.org/10.1186/s41544-019-0005-1] [PMID: 34171007]
[34]
Shah MY, Ferrajoli A, Sood AK, Lopez-Berestein G, Calin GA. microRNA therapeutics in cancer—an emerging concept. EBioMedicine 2016; 12: 34-42.
[http://dx.doi.org/10.1016/j.ebiom.2016.09.017] [PMID: 27720213]
[35]
van Solingen C, Seghers L, Bijkerk R, et al. Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis. J Cell Mol Med 2009; 13(8a): 1577-85.
[http://dx.doi.org/10.1111/j.1582-4934.2008.00613.x] [PMID: 19120690]
[36]
Ebert MS, Sharp PA. MicroRNA sponges: Progress and possibilities. RNA 2010; 16(11): 2043-50.
[http://dx.doi.org/10.1261/rna.2414110] [PMID: 20855538]
[37]
Fu Y, Chen J, Huang Z. Recent progress in microRNA-based delivery systems for the treatment of human disease. ExRNA 2019; 1(1): 24.
[http://dx.doi.org/10.1186/s41544-019-0024-y] [PMID: 34171007]
[38]
Bader AG, Brown D, Winkler M. The promise of microRNA replacement therapy. Cancer Res 2010; 70(18): 7027-30.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2010] [PMID: 20807816]
[39]
Abd-Aziz N, Kamaruzman NI, Poh CL. Development of microRNAs as potential therapeutics against cancer. J Oncol 2020; 2020: 1-14.
[http://dx.doi.org/10.1155/2020/8029721] [PMID: 32733559]
[40]
Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CMP. Delivering the promise of miRNA cancer therapeutics. Drug Discov Today 2013; 18(5-6): 282-9.
[http://dx.doi.org/10.1016/j.drudis.2012.10.002] [PMID: 23064097]
[41]
Peplow PV, Martinez B. MicroRNAs in Parkinson’s disease and emerging therapeutic targets. Neural Regen Res 2017; 12(12): 1945-59.
[http://dx.doi.org/10.4103/1673-5374.221147] [PMID: 29323027]
[42]
Paul S, Bravo Vázquez LA, Pérez Uribe S, Roxana Reyes-Pérez P, Sharma A. Current status of microRNA-based therapeutic approaches in neurodegenerative disorders. Cells 2020; 9(7): 1698.
[http://dx.doi.org/10.3390/cells9071698] [PMID: 32679881]
[43]
Kotowska-Zimmer A, Pewinska M, Olejniczak M. Artificial miRNAs as therapeutic tools: Challenges and opportunities. Wiley Interdiscip Rev RNA 2021; 12(4): e1640.
[http://dx.doi.org/10.1002/wrna.1640] [PMID: 33386705]
[44]
Walayat A, Yang M, Xiao D. Therapeutic implication of miRNA in human disease. In: Antisense therapy 2022.
[45]
Leclercq M, Diallo AB, Blanchette M. Prediction of human miRNA target genes using computationally reconstructed ancestral mammalian sequences. Nucleic Acids Res 2017; 45(2): 556-66.
[http://dx.doi.org/10.1093/nar/gkw1085] [PMID: 27899600]
[46]
Christopher AF, Gupta M, Bansal P. Micronome revealed miR-19a/b as key regulator of SOCS3 during cancer related inflammation of oral squamous cell carcinoma. Gene 2016; 594(1): 30-40.
[http://dx.doi.org/10.1016/j.gene.2016.08.044] [PMID: 27581787]
[47]
Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol 2011; 30(1): 16-34.
[http://dx.doi.org/10.3109/08830185.2010.529976] [PMID: 21235323]
[48]
Sledz CA, Holko M, de Veer MJ, Silverman RH, Williams BRG. Activation of the interferon system by short-interfering RNAs. Nat Cell Biol 2003; 5(9): 834-9.
[http://dx.doi.org/10.1038/ncb1038] [PMID: 12942087]
[49]
Barton GM, Medzhitov R. Toll-like receptor signaling pathways. Science 2003; 300(5625): 1524-5.
[http://dx.doi.org/10.1126/science.1085536] [PMID: 12791976]
[50]
Sioud M. Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts: A central role for 2′-hydroxyl uridines in immune responses. Eur J Immunol 2006; 36(5): 1222-30.
[http://dx.doi.org/10.1002/eji.200535708] [PMID: 16609928]
[51]
Judge AD, Bola G, Lee ACH, MacLachlan I. Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol Ther 2006; 13(3): 494-505.
[http://dx.doi.org/10.1016/j.ymthe.2005.11.002] [PMID: 16343994]
[52]
Artegiani B, Clevers H. Use and application of 3D-organoid technology. Hum Mol Genet 2018; 27(R2): R99-R107.
[http://dx.doi.org/10.1093/hmg/ddy187] [PMID: 29796608]
[53]
Aparicio S, Hidalgo M, Kung AL. Examining the utility of patient-derived xenograft mouse models. Nat Rev Cancer 2015; 15(5): 311-6.
[http://dx.doi.org/10.1038/nrc3944] [PMID: 25907221]
[54]
Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 2014; 42(D1): D68-73.
[http://dx.doi.org/10.1093/nar/gkt1181] [PMID: 24275495]
[55]
Kleinman ME, Yamada K, Takeda A, et al. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 2008; 452(7187): 591-7.
[http://dx.doi.org/10.1038/nature06765] [PMID: 18368052]
[56]
Dalpke AH, Helm M. RNA mediated toll-like receptor stimulation in health and disease. RNA Biol 2012; 9(6): 828-42.
[http://dx.doi.org/10.4161/rna.20206] [PMID: 22617878]
[57]
Obad S, dos Santos CO, Petri A, et al. Silencing of microRNA families by seed-targeting tiny LNAs. Nat Genet 2011; 43(4): 371-8.
[http://dx.doi.org/10.1038/ng.786] [PMID: 21423181]
[58]
Cortez MA, Anfossi S, Ramapriyan R, et al. Role of miRNAs in immune responses and immunotherapy in cancer. Genes Chromosomes Cancer 2019; 58(4): 244-53.
[http://dx.doi.org/10.1002/gcc.22725] [PMID: 30578699]
[59]
Smolle MA, Calin HN, Pichler M, Calin GA. Noncoding RNAs and immune checkpoints-clinical implications as cancer therapeutics. FEBS J 2017; 284(13): 1952-66.
[http://dx.doi.org/10.1111/febs.14030] [PMID: 28132417]
[60]
Cruz De los Santos M, Dragomir MP, Calin GA. The role of exosomal long non-coding RNAs in cancer drug resistance. Cancer Drug Resist 2019; 2(4): 1178-92.
[http://dx.doi.org/10.20517/cdr.2019.74] [PMID: 31867576]
[61]
Egli M, Manoharan M. Re-engineering RNA molecules into therapeutic agents. Acc Chem Res 2019; 52(4): 1036-47.
[http://dx.doi.org/10.1021/acs.accounts.8b00650] [PMID: 30912917]
[62]
Crooke ST, Seth PP, Vickers TA, Liang X. The interaction of phosphorothioate-containing RNA targeted drugs with proteins is a critical determinant of the therapeutic effects of these agents. J Am Chem Soc 2020; 142(35): 14754-71.
[http://dx.doi.org/10.1021/jacs.0c04928] [PMID: 32786803]
[63]
Winkle M, El-Daly SM, Fabbri M, Calin GA. Noncoding RNA therapeutics — challenges and potential solutions. Nat Rev Drug Discov 2021; 20(8): 629-51.
[http://dx.doi.org/10.1038/s41573-021-00219-z] [PMID: 34145432]
[64]
Rigoutsos I, Lee SK, Nam SY, et al. N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration. Genome Biol 2017; 18(1): 98.
[http://dx.doi.org/10.1186/s13059-017-1224-0] [PMID: 28535802]
[65]
Avitabile C, Saviano M, D’Andrea L, et al. Targeting pre-miRNA by peptide nucleic acids: a new strategy to interfere in the miRNA maturation. Artif DNA PNA XNA 2012; 3(2): 88-96.
[http://dx.doi.org/10.4161/adna.20911] [PMID: 22699795]
[66]
Avitabile C, Fabbri E, Bianchi N, Gambari R, Romanelli A. Inhibition of miRNA maturation by peptide nucleic acids. Methods Mol Biol 2014; 1095: 157-64.
[http://dx.doi.org/10.1007/978-1-62703-703-7_13] [PMID: 24166311]
[67]
Chew WL. Immunity to CRISPR Cas9 and Cas12a therapeutics. Wiley Interdiscip Rev Syst Biol Med 2018; 10(1): e1408.
[http://dx.doi.org/10.1002/wsbm.1408] [PMID: 29083112]
[68]
Zhou Y, Zhou G, Tian C, et al. Exosome‐mediated small RNA delivery for gene therapy. Wiley Interdiscip Rev RNA 2016; 7(6): 758-71.
[http://dx.doi.org/10.1002/wrna.1363] [PMID: 27196002]
[69]
Bayraktar R, Van Roosbroeck K, Calin GA. Cell‐to‐cell communication: microRNAs as hormones. Mol Oncol 2017; 11(12): 1673-86.
[http://dx.doi.org/10.1002/1878-0261.12144] [PMID: 29024380]
[70]
Hu B, Zhong L, Weng Y, et al. Therapeutic siRNA: state of the art. Signal Transduct Target Ther 2020; 5(1): 101.
[http://dx.doi.org/10.1038/s41392-020-0207-x] [PMID: 32561705]
[71]
Weng Y, Xiao H, Zhang J, Liang XJ, Huang Y. RNAi therapeutic and its innovative biotechnological evolution. Biotechnol Adv 2019; 37(5): 801-25.
[http://dx.doi.org/10.1016/j.biotechadv.2019.04.012] [PMID: 31034960]
[72]
Jansson MD, Lund AH. MicroRNA and cancer. Mol Oncol 2012; 6(6): 590-610.
[http://dx.doi.org/10.1016/j.molonc.2012.09.006] [PMID: 23102669]
[73]
Stenvang J, Petri A, Lindow M, Obad S, Kauppinen S. Inhibition of microRNA function by antimiR oligonucleotides. Silence 2012; 3(1): 1-7.
[http://dx.doi.org/10.1186/1758-907X-3-1] [PMID: 22230293]
[74]
Kinoshita C, Kikuchi-Utsumi K, Aoyama K, et al. Inhibition of miR-96-5p in the mouse brain increases glutathione levels by altering NOVA1 expression. Commun Biol 2021; 4(1): 182.
[http://dx.doi.org/10.1038/s42003-021-01706-0] [PMID: 33568779]
[75]
Lin Q, Mao Y, Song Y, Huang D. MicroRNA-34a induces apoptosis in PC12 cells by reducing B-cell lymphoma 2 and sirtuin-1 expression. Mol Med Rep 2015; 12(4): 5709-14.
[http://dx.doi.org/10.3892/mmr.2015.4185] [PMID: 26252661]
[76]
Trang P, Wiggins JF, Daige CL, et al. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther 2011; 19(6): 1116-22.
[http://dx.doi.org/10.1038/mt.2011.48] [PMID: 21427705]
[77]
Carlsson L, Clarke JC, Yen C, et al. Biocompatible, purified VEGF-A mRNA improves cardiac function after intracardiac injection 1-week post-myocardial infarction in swine. Mol Ther Methods Clin Dev 2018; 9: 330-46.
[http://dx.doi.org/10.1016/j.omtm.2018.04.003] [PMID: 30038937]
[78]
Damase TR, Sukhovershin R, Boada C, Taraballi F, Pettigrew RI, Cooke JP. The Limitless Future of RNA Therapeutics. Front Bioeng Biotechnol 2021; 9: 628137.
[http://dx.doi.org/10.3389/fbioe.2021.628137] [PMID: 33816449]
[79]
mRNA Therapeutics and Vaccines | Translate Bio | Pipeline Transl. Bio. 2019. Available from: https://translate.bio/pipeline/ (Accessed on: February 25, 2022).
[80]
Moderna’s mRNA Clinical Trials: CMV, MMA, Zika, Several Types of Cancer and Other Diseases. 2021. Available from: https://www.modernatx.com/pipeline/modernas-mrna-clinical-trials-cmvmma-zika-several-types-cancer-and-other-diseases (Accessed on: January 27, 2021).

Rights & Permissions Print Cite
Article Metrics
24
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy