Using RNAi in the treatment of cardiovascular diseases - therapeutics based on siRNA overview
DOI:
https://doi.org/10.12775/JEHS.2022.12.07.089Keywords
RNAi, RNA interference, siRNA, RNA, therapeutics, cardiovascular diseasesAbstract
RNA interference (RNAi) discovered in the 1990s by Fire and Mello plays a role in silencing gene function. One type of RNAi is siRNA, which is a double-stranded molecule of 20-25 base pairs. This molecule is made by cleaving double-stranded RNA by the enzyme Dicer. siRNA binds to the protein complex with ribonuclease activity - RISC (RNA-induced silencing complex). The resulting complex binds to the mRNA and cuts it into parts, which blocks the formation of the protein encoded by the mRNA. This property has been exploited in the production of siRNA-based drugs. However, the instability of siRNA molecules turned out to be difficult - the challenge was to properly modify the structure of siRNA in order to increase the stability and half-life and select the appropriate method of delivering the molecule to the body. Many siRNA-based drugs have already been developed, but most are in clinical trials. In this review, we present the role of RNA interference in therapeutics production and use of siRNA in cardiovascular diseases treatment.
References
Liang X, Li D, Leng S, Zhu X. RNA-based pharmacotherapy for tumors: From bench to clinic and back. Biomed Pharmacother. 2020 May;125:109997. doi: 10.1016/j.biopha.2020.109997. Epub 2020 Feb 13. PMID: 32062550.
Wilson RC, Doudna JA. Molecular mechanisms of RNA interference. Annu Rev Biophys. 2013;42:217-39. doi: 10.1146/annurev-biophys-083012-130404. PMID: 23654304; PMCID: PMC5895182.
Caillaud M, El Madani M, Massaad-Massade L. Small interfering RNA from the lab discovery to patients' recovery. J Control Release. 2020 May 10;321:616-628. doi: 10.1016/j.jconrel.2020.02.032. Epub 2020 Feb 19. PMID: 32087301.
Weng Y, Li C, Yang T, Hu B, Zhang M, Guo S, Xiao H, Liang XJ, Huang Y. The challenge and prospect of mRNA therapeutics landscape. Biotechnol Adv. 2020 May-Jun;40:107534. doi: 10.1016/j.biotechadv.2020.107534. Epub 2020 Feb 21. PMID: 32088327.
Dong Y, Siegwart DJ, Anderson DG. Strategies, design, and chemistry in siRNA delivery systems. Adv Drug Deliv Rev. 2019 Apr;144:133-147. doi: 10.1016/j.addr.2019.05.004. Epub 2019 May 15. PMID: 31102606; PMCID: PMC6745264.
Speiser JJ, Erşahin C, Osipo C. The functional role of Notch signaling in triple-negative breast cancer. Vitam Horm. 2013;93:277-306. doi: 10.1016/B978-0-12-416673-8.00013-7. PMID: 23810012.
Lee LW, Zhang S, Etheridge A, Ma L, Martin D, Galas D, Wang K. Complexity of the microRNA repertoire revealed by next-generation sequencing. RNA. 2010 Nov;16(11):2170-80. doi: 10.1261/rna.2225110. Epub 2010 Sep 28. PMID: 20876832; PMCID: PMC2957056.
Bejar N, Tat TT, Kiss DL. RNA Therapeutics: the Next Generation of Drugs for Cardiovascular Diseases. Curr Atheroscler Rep. 2022 May;24(5):307-321. doi: 10.1007/s11883-022-01007-9. Epub 2022 Apr 2. PMID: 35364795; PMCID: PMC8975710.
Langer C, Rücker FG, Buske C, Döhner H, Kuchenbauer F. Targeted therapies through microRNAs: pulp or fiction? Ther Adv Hematol. 2012 Apr;3(2):97-104. doi: 10.1177/2040620711432582. PMID: 23556116; PMCID: PMC3573433.
Zhao Z, Lin CY, Cheng K. siRNA- and miRNA-based therapeutics for liver fibrosis. Transl Res. 2019 Dec;214:17-29. doi: 10.1016/j.trsl.2019.07.007. Epub 2019 Aug 13. PMID: 31476281; PMCID: PMC6848786.
Thermo Fisher Scientific. Delivering RNAi to Cells - Transfection and Viral Delivery. https://www.thermofisher.com/pl/en/home/life-science/rnai/delivering-rnai-to-cells-transfection-and-viral-delivery.html.html (14.07.2022)
Dowdy SF. Overcoming cellular barriers for RNA therapeutics. Nat Biotechnol. 2017 Mar;35(3):222-229. doi: 10.1038/nbt.3802. Epub 2017 Feb 27. PMID: 28244992.
Sun Y, Zhao Y, Zhao X, Lee RJ, Teng L, Zhou C. Enhancing the Therapeutic Delivery of Oligonucleotides by Chemical Modification and Nanoparticle Encapsulation. Molecules. 2017 Oct 13;22(10):1724. doi: 10.3390/molecules22101724. PMID: 29027965; PMCID: PMC6158866.
Zhang MM, Bahal R, Rasmussen TP, Manautou JE, Zhong XB. The growth of siRNA-based therapeutics: Updated clinical studies. Biochem Pharmacol. 2021 Jul;189:114432. doi: 10.1016/j.bcp.2021.114432. Epub 2021 Jan 26. PMID: 33513339; PMCID: PMC8187268.
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 Sep 15;8:132-143. doi: 10.1016/j.omtn.2017.06.005. Epub 2017 Jun 12. PMID: 28918016; PMCID: PMC5496203.
Latimer J, Batty JA, Neely RD, Kunadian V. PCSK9 inhibitors in the prevention of cardiovascular disease. J Thromb Thrombolysis. 2016 Oct;42(3):405-19. doi: 10.1007/s11239-016-1364-1. Erratum in: J Thromb Thrombolysis. 2016 Oct;42(3):420. PMID: 27095708; PMCID: PMC5010583.
Dyrbuś K, Gąsior M, Penson P, Ray KK, Banach M. Inclisiran-New hope in the management of lipid disorders? J Clin Lipidol. 2020 Jan-Feb;14(1):16-27. doi: 10.1016/j.jacl.2019.11.001. Epub 2019 Nov 12. PMID: 31879073.
Kosmas CE, Muñoz Estrella A, Sourlas A, Silverio D, Hilario E, Montan PD, Guzman E. Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia. Diseases. 2018 Jul 13;6(3):63. doi: 10.3390/diseases6030063. PMID: 30011788; PMCID: PMC6163360.
Debacker AJ, Voutila J, Catley M, Blakey D, Habib N. Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug. Mol Ther. 2020 Aug 5;28(8):1759-1771. doi: 10.1016/j.ymthe.2020.06.015. Epub 2020 Jun 17. PMID: 32592692; PMCID: PMC7403466.
Lamb YN. Inclisiran: First Approval. Drugs. 2021 Feb;81(3):389-395. doi: 10.1007/s40265-021-01473-6. Erratum in: Drugs. 2021 Jun;81(9):1129. PMID: 33620677; PMCID: PMC7900795.
Rogula S, Błażejowska E, Gąsecka A, Szarpak Ł, Jaguszewski MJ, Mazurek T, Filipiak KJ. Inclisiran-Silencing the Cholesterol, Speaking up the Prognosis. J Clin Med. 2021 Jun 2;10(11):2467. doi: 10.3390/jcm10112467. PMID: 34199468; PMCID: PMC8199585.
Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Planté-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):11-21. doi: 10.1056/NEJMoa1716153. PMID: 29972753.
Clinical Trials. APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy) https://www.clinicaltrials.gov/ct2/show/NCT03997383 (16.07.2022)
Clinical Trials Arena. Vutrisiran HELIOS-A results bolster its FDA application https://www.clinicaltrialsarena.com/comment/vutrisiran-results-fda-application/ (16.07.2022)
Majeed CN, Ma CD, Xiao T, Rudnick S, Bonkovsky HL. Spotlight on Givosiran as a Treatment Option for Adults with Acute Hepatic Porphyria: Design, Development, and Place in Therapy. Drug Des Devel Ther. 2022 Jun 16;16:1827-1845. doi: 10.2147/DDDT.S281631. PMID: 35734365; PMCID: PMC9208469.
Lazareth H, Poli A, Bignon Y, Mirmiran A, Rabant M, Cohen R, Schmitt C, Puy H, Karras A, Gouya L, Pallet N. Renal Function Decline With Small Interfering RNA Silencing Aminolevulinic Acid Synthase 1 (ALAS1). Kidney Int Rep. 2021 Apr 15;6(7):1904-1911. doi: 10.1016/j.ekir.2021.04.004. PMID: 34307985; PMCID: PMC8258458.
Pasi KJ, Lissitchkov T, Mamonov V, Mant T, Timofeeva M, Bagot C, Chowdary P, Georgiev P, Gercheva-Kyuchukova L, Madigan K, Van Nguyen H, Yu Q, Mei B, Benson CC, Ragni MV. Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran-Results of the phase 1 inhibitor cohort. J Thromb Haemost. 2021 Jun;19(6):1436-1446. doi: 10.1111/jth.15270. Epub 2021 May 18. PMID: 33587824; PMCID: PMC8251589.
Thielmann M, Corteville D, Szabo G, Swaminathan M, Lamy A, Lehner LJ, Brown CD, Noiseux N, Atta MG, Squiers EC, Erlich S, Rothenstein D, Molitoris B, Mazer CD. Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study. Circulation. 2021 Oct 5;144(14):1133-1144. doi: 10.1161/CIRCULATIONAHA.120.053029. Epub 2021 Sep 3. PMID: 34474590; PMCID: PMC8487715.
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