Login Register Cart 0
Review Article

Current RNA-based Therapeutics in Clinical Trials

Author(s): Ling-Yan Zhou, Zhou Qin, Yang-Hui Zhu, Zhi-Yao He* and Ting Xu*

Volume 19, Issue 3, 2019

Page: [172 - 196] Pages: 25

DOI: 10.2174/1566523219666190719100526

Price: $65

Abstract

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

Keywords: Antisense oligonucleotide, small interfering RNA, microRNA, small activating RNA, ribozyme, aptamer, messenger RNA, single guide RNA.

« Previous Next »
Graphical Abstract

[1]
Cech TR, Steitz JA. The noncoding RNA revolution-trashing old rules to forge new ones. Cell 2014; 157(1): 77-94.
[http://dx.doi.org/10.1016/j.cell.2014.03.008] [PMID: 24679528]
[2]
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nat 1998; 391(6669): 806-11.
[http://dx.doi.org/10.1038/35888] [PMID: 9486653]
[3]
Guerrier-Takada C, Gardiner K, Marsh T, Pace N, Altman S. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 1983; 35(3 Pt 2): 849-57.
[http://dx.doi.org/10.1016/0092-8674(83)90117-4] [PMID: 6197186]
[4]
Melnikova I. RNA-based therapies. Nat Rev Drug Discov 2007; 6(11): 863-4.
[http://dx.doi.org/10.1038/nrd2443]
[5]
Russ AP, Lampel S. The druggable genome: An update. Drug Discov Today 2005; 10(23-24): 1607-10.
[http://dx.doi.org/10.1016/S1359-6446(05)03666-4] [PMID: 16376820]
[6]
Lieberman J. Tapping the RNA world for therapeutics. Nat Struct Mol Biol 2018; 25(5): 357-64.
[http://dx.doi.org/10.1038/s41594-018-0054-4] [PMID: 29662218]
[7]
Verdine GL, Walensky LD. The challenge of drugging undruggable targets in cancer: Lessons learned from targeting BCL-2 family members. Clin Cancer Res 2007; 13(24): 7264-70.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-2184] [PMID: 18094406]
[8]
Sanghvi YS. A status updates of modified oligonucleotides for chemotherapeutics applications Curr Protoc Nucl Acid Chem 1- 22 2011.;
[http://dx.doi.org/10.1002/0471142700.nc0401s46]
[9]
Shukla S, Sumaria CS, Pradeepkumar PI. Exploring chemical modifications for siRNA therapeutics: A structural and functional outlook. ChemMedChem 2010; 5(3): 328-49.
[http://dx.doi.org/10.1002/cmdc.200900444] [PMID: 20043313]
[10]
Stein CA, Castanotto D. FDA-approved oligonucleotide therapies in 2017. Mol Ther 2017; 25(5): 1069-75.
[http://dx.doi.org/10.1016/j.ymthe.2017.03.023] [PMID: 28366767]
[11]
Wood H. FDA approves patisiran to treat hereditary transthyretin amyloidosis. Nat Rev Neurol 2018; 14(10): 570.
[http://dx.doi.org/10.1038/s41582-018-0065-0] [PMID: 30158559]
[12]
Seth PP, Tanowitz M, Bennett CF. Selective tissue targeting of synthetic nucleic acid drugs. J Clin Invest 2019; 129(3): 915-25.
[http://dx.doi.org/10.1172/JCI125228] [PMID: 30688661]
[13]
Aagaard L, Rossi JJ. RNAi therapeutics: principles, prospects and challenges. Adv Drug Deliv Rev 2007; 59(2-3): 75-86.
[http://dx.doi.org/10.1016/j.addr.2007.03.005] [PMID: 17449137]
[14]
Liang XH, Shen W, Sun H, Migawa MT, Vickers TA, Crooke ST. Translation efficiency of mRNAs is increased by antisense oligonucleotides targeting upstream open reading frames. Nat Biotechnol 2016; 34(8): 875-80.
[http://dx.doi.org/10.1038/nbt.3589] [PMID: 27398791]
[15]
Young CS, Pyle AD. Exon skipping therapy. Cell 2016; 167(5): 1144.
[http://dx.doi.org/10.1016/j.cell.2016.10.050] [PMID: 27863231]
[16]
Crooke ST. Molecular mechanisms of antisense oligonucleotides. Nucleic Acid Ther 2017; 27(2): 70-7.
[http://dx.doi.org/10.1089/nat.2016.0656] [PMID: 28080221]
[17]
Linnane E, Davey P, Zhang P, et al. Differential uptake, kinetics and mechanisms of intracellular trafficking of next-generation antisense oligonucleotides across human cancer cell lines. Nucleic Acids Res 2019; 47(9): 4375-92.
[http://dx.doi.org/10.1093/nar/gkz214] [PMID: 30927008]
[18]
Keam SJ. Inotersen: First global approval. Drugs 2018; 78(13): 1371-6.
[http://dx.doi.org/10.1007/s40265-018-0968-5] [PMID: 30120737]
[19]
Den Hollander AI, Koenekoop RK, Yzer S, et al. Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. Am J Hum Genet 2006; 79(3): 556-61.
[http://dx.doi.org/10.1086/507318] [PMID: 16909394]
[20]
Gerard X, Perrault I, Hanein S, et al. Aon-mediated exon skipping restores ciliation in fibroblasts harboring the common leber congenital amaurosis cep290 mutation. A Hum Gene Ther 2012; 23(10): 556-61.
[http://dx.doi.org/10.1038/mtna.2012.21]
[21]
Dulla K, Aguila M, Lane A, et al. Splice-modulating oligonucleotide qr-110 restores cep290 mrna and function in human c.2991+1655a > g lca10 models. Mol Ther Nucleic Acids 2018; 12: 730-40.
[http://dx.doi.org/10.1016/j.omtn.2018.07.010] [PMID: 30114557]
[22]
Henig N, Beumer W, Anthonijsz H, et al. Qr-010, an RNA therapy, restores CFTR function in the saliva secretion assay. Am J Respir Crit Care Med 2015; 191: A1449.
[23]
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998; 391(6669): 806-11.
[http://dx.doi.org/10.1038/35888] [PMID: 9486653]
[24]
Fellmann C, Lowe SW. Stable RNA interference rules for silencing. Nat Cell Biol 2014; 16(1): 10-8.
[http://dx.doi.org/10.1038/ncb2895] [PMID: 24366030]
[25]
Matranga C, Tomari Y, Shin C, Bartel DP, Zamore PD. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 2005; 123(4): 607-20.
[http://dx.doi.org/10.1016/j.cell.2005.08.044] [PMID: 16271386]
[26]
Meister G, Tuschl T. Mechanisms of gene silencing by double-stranded RNA. Nature 2004; 431(7006): 343-9.
[http://dx.doi.org/10.1038/nature02873] [PMID: 15372041]
[27]
Dejneka NS, Wan SH, Bond OS, Kornbrust DJ, Reich SJ. Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes Mol Vis 2008; 14(116-19). : 997-1005.
[PMID: 18523657]
[28]
https://www.alnylam.com/2012/09/04/complete-results-of-our-aln-rsv01-phase-iib-study/
[29]
Leachman SA, Hickerson RP, Hull PR, et al. Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita. J Dermatol Sci 2008; 51(3): 151-7.
[http://dx.doi.org/10.1016/j.jdermsci.2008.04.003] [PMID: 18495438]
[30]
Leachman SA, Kaspar RL, Fleckman P, et al. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10(1): 3-17.
[http://dx.doi.org/10.1111/j.1087-0024.2005.10202.x] [PMID: 16250204]
[31]
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]
[32]
Benitez-Del-Castillo JM, Moreno-Montañés J, Jiménez-Alfaro I, et al. Safety and efficacy clinical trials for syl1001, a novel short interfering RNA for the treatment of dry eye disease. Invest Ophthalmol Vis Sci 2016; 57(14): 6447-54.
[http://dx.doi.org/10.1167/iovs.16-20303] [PMID: 27893109]
[33]
Peer D, Lieberman J. Special delivery: Targeted therapy with small RNAs. Gene Ther 2011; 18(12): 1127-33.
[http://dx.doi.org/10.1038/gt.2011.56] [PMID: 21490679]
[34]
Thompson JD, Kornbrust DJ, Foy JW, et al. Toxicological and pharmacokinetic properties of chemically modified siRNAs targeting p53 RNA following intravenous administration. Nucleic Acid Ther 2012; 22(4): 255-64.
[http://dx.doi.org/10.1089/nat.2012.0371] [PMID: 22913596]
[35]
Bartlett DW, Su H, Hildebrandt IJ, Weber WA, Davis ME. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc Natl Acad Sci USA 2007; 104(39): 15549-54.
[http://dx.doi.org/10.1073/pnas.0707461104] [PMID: 17875985]
[36]
Zuckerman JE, Gritli I, Tolcher A, et al. Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA. Proc Natl Acad Sci USA 2014; 111(31): 11449-54.
[http://dx.doi.org/10.1073/pnas.1411393111] [PMID: 25049380]
[37]
Morrissey DV, Lockridge JA, Shaw L, et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 2005; 23(8): 1002-7.
[http://dx.doi.org/10.1038/nbt1122] [PMID: 16041363]
[38]
El Dika I, Lim HY, Yong WP, et al. An open-label, multicenter, phase I, dose escalation study with phase II expansion cohort to determine the safety, pharmacokinetics, and preliminary antitumor activity of intravenous tkm-080301 in subjects with advanced hepatocellular carcinoma. Oncol 2019; 24(6): 747-e218.
[http://dx.doi.org/10.1634/theoncologist.2018-0838] [PMID: 30598500]
[39]
Hoy SM. Patisiran: First global approval. Drugs 2018; 78(15): 1625-31.
[http://dx.doi.org/10.1007/s40265-018-0983-6] [PMID: 30251172]
[40]
Kristen AV, Ajroud-Driss S, Conceição I, Gorevic P, Kyriakides T, Obici L. Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis. Neuro Dis Manag 2019; 9(1): 5-23.
[http://dx.doi.org/10.2217/nmt-2018-0033] [PMID: 30480471]
[41]
Al Shaer D, Al Musaimi O, Albericio F, de la Torre BG. 2018 FDA tides harvest. Pharmacy (Basel) 2019; 12(2)E52
[http://dx.doi.org/10.3390/ph12020052] [PMID: 30959752]
[42]
Kanasty R, Dorkin JR, Vegas A, Anderson D. Delivery materials for siRNA therapeutics. Nat Mater 2013; 12(11): 967-77.
[http://dx.doi.org/10.1038/nmat3765] [PMID: 24150415]
[43]
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Sci 2001; 294(5543): 853-8.
[http://dx.doi.org/10.1126/science.1064921] [PMID: 11679670]
[44]
Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004; 116(2): 281-97.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[45]
Shukla GC, Singh J, Barik S. Micrornas: Processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol 2011; 3(3): 83-92.
[PMID: 22468167]
[46]
Lima JF, Cerqueira L, Figueiredo C, Oliveira C, Azevedo NF. Anti-miRNA oligonucleotides: A comprehensive guide for design. RNA Biol 2018; 15(3): 338-52.
[http://dx.doi.org/10.1080/15476286.2018.1445959] [PMID: 29570036]
[47]
Mendell JT, Olson EN. MicroRNAs in stress signaling and human disease. Cell 2012; 148(6): 1172-87.
[http://dx.doi.org/10.1016/j.cell.2012.02.005] [PMID: 22424228]
[48]
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]
[49]
Rupaimoole R, Slack FJ. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 2017; 16(3): 203-22.
[http://dx.doi.org/10.1038/nrd.2016.246] [PMID: 28209991]
[50]
Broderick JA, Zamore PD. MicroRNA therapeutics. Gene Ther 2011; 18(12): 1104-10.
[http://dx.doi.org/10.1038/gt.2011.50] [PMID: 21525952]
[51]
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]
[52]
Ottosen S, Parsley TB, Yang L, et al. In vitro antiviral activity and preclinical and clinical resistance profile of miravirsen, a novel anti-hepatitis C virus therapeutic target the human factor miR-122. Antimicrob Agents Chemother 2015; 59(1): 599-608.
[http://dx.doi.org/10.1128/AAC.04220-14] [PMID: 25385103]
[53]
Van der Ree MH, van der Meer AJ, de Bruijne J, et al. Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients. Antiviral Res 2014; 111: 53-9.
[http://dx.doi.org/10.1016/j.antiviral.2014.08.015] [PMID: 25218783]
[54]
Stelma F, van der Ree MH, Sinnige MJ, et al. Immune phenotype and function of natural killer and T cells in chronic hepatitis C patients who received a single dose of anti-MicroRNA-122, RG-101. Hepatology 2017; 66(1): 57-68.
[http://dx.doi.org/10.1002/hep.29148] [PMID: 28295463]
[55]
Seto AG, Beatty X, Lynch JM, et al. Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma. Br J Haematol 2018; 183(3): 428-44.
[http://dx.doi.org/10.1111/bjh.15547] [PMID: 30125933]
[56]
Gallant-Behm CL, Piper J, Lynch JM, et al. A microrna-29 mimic (remlarsen) represses extracellular matrix expression and fibroplasia in the skin. J Invest Dermatol 2019; 139(5): 1073-81.
[http://dx.doi.org/10.1016/j.jid.2018.11.007] [PMID: 30472058]
[57]
Bader AG. miR-34 - a microRNA replacement therapy is headed to the clinic. Front Genet 2012; 3: 120.
[http://dx.doi.org/10.3389/fgene.2012.00120] [PMID: 22783274]
[58]
He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature 2007; 447(7148): 1130-4.
[http://dx.doi.org/10.1038/nature05939] [PMID: 17554337]
[59]
Beg MS, Brenner AJ, Sachdev J, et al. Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Invest New Drugs 2017; 35(2): 180-8.
[http://dx.doi.org/10.1007/s10637-016-0407-y] [PMID: 27917453]
[60]
Usman N, Blatt LM. Nuclease-resistant synthetic ribozymes: Developing a new class of therapeutics. J Clin Invest 2000; 106(10): 1197-202.
[http://dx.doi.org/10.1172/JCI11631] [PMID: 11086019]
[61]
Karpel-Massler G, Wirtz CR, Halatsch M-E. Ribozyme-mediated inhibition of 801-bp deletion-mutant epidermal growth factor receptor mRNA expression in glioblastoma multiforme. Molecules 2010; 15(7): 4670-8.
[http://dx.doi.org/10.3390/molecules15074670] [PMID: 20657384]
[62]
Reymond C, Beaudoin J-D, Perreault J-P. Modulating RNA structure and catalysis: lessons from small cleaving ribozymes. Cell Mol Life Sci 2009; 66(24): 3937-50.
[http://dx.doi.org/10.1007/s00018-009-0124-1] [PMID: 19718544]
[63]
Mulhbacher J, St-Pierre P, Lafontaine DA. Therapeutic applications of ribozymes and riboswitches. Curr Opin Pharmacol 2010; 10(5): 551-6.
[http://dx.doi.org/10.1016/j.coph.2010.07.002] [PMID: 20685165]
[64]
Kobayashi H, Eckhardt SG, Lockridge JA, et al. Safety and pharmacokinetic study of RPI.4610 (ANGIOZYME), an anti-VEGFR-1 ribozyme, in combination with carboplatin and paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol 2005; 56(4): 329-36.
[http://dx.doi.org/10.1007/s00280-004-0968-x] [PMID: 15906031]
[65]
Weng DE, Masci PA, Radka SF, et al. A phase I clinical trial of a ribozyme-based angiogenesis inhibitor targeting vascular endothelial growth factor receptor-1 for patients with refractory solid tumors. Mol Cancer Ther 2005; 4(6): 948-55.
[http://dx.doi.org/10.1158/1535-7163.MCT-04-0210] [PMID: 15956252]
[66]
Morrow PK, Murthy RK, Ensor JD, et al. An open-label, phase 2 trial of RPI.4610 (Angiozyme) in the treatment of metastatic breast cancer. Cancer 2012; 118(17): 4098-104.
[http://dx.doi.org/10.1002/cncr.26730] [PMID: 22281842]
[67]
Tong M, Schiff E, Jensen DM, et al. Preliminary analysis of a phase II study of heptazyme (tm), a nuclease resistant ribozyme targeting hepatitis c virus (hcv) rna. Hepatology 2002; 36(4 pt 2): 788.
[68]
Sandberg JA, Rossi SJ, Gordon GS, et al. Safety analysis of a phase I study of heptazyme (tm), a nuclease resistant ribozyme targeting hepatitis c (hcv) rna. Hepatology 2001; 34(4 Pt 2): 646.
[69]
Wolff JA, Malone RW, Williams P, et al. Direct gene transfer into mouse muscle in vivo. Science 1990; 247(4949 Pt 1): 1465-8.
[http://dx.doi.org/10.1126/science.1690918] [PMID: 1690918]
[70]
Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics--developing a new class of drugs. Nat Rev Drug Discov 2014; 13(10): 759-80.
[http://dx.doi.org/10.1038/nrd4278] [PMID: 25233993]
[71]
Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov 2018; 17(4): 261-79.
[http://dx.doi.org/10.1038/nrd.2017.243] [PMID: 29326426]
[72]
Wong G, Gao GF. An mRNA-based vaccine strategy against Zika. Cell Res 2017; 27(9): 1077-8.
[http://dx.doi.org/10.1038/cr.2017.53] [PMID: 28397799]
[73]
Lundstrom K. Latest development on RNA-based drugs and vaccines. Futur Sci OA 2018; 4(5)FSO300.
[http://dx.doi.org/10.4155/fsoa-2017-0151] [PMID: 29796303]
[74]
Grunwitz C, Kranz LM. mRNA cancer vaccines-messages that prevail. Curr Top Microbiol Immunol 2017; 405: 145-64.
[http://dx.doi.org/10.1007/82_2017_509] [PMID: 28401358]
[75]
Wykes M, Pombo A, Jenkins C, MacPherson GG. Dendritic cells interact directly with naive B lymphocytes to transfer antigen and initiate class switching in a primary T-dependent response. J Immunol 1998; 161(3): 1313-9.
[PMID: 9686593]
[76]
Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 1996; 2(1): 52-8.
[http://dx.doi.org/10.1038/nm0196-52] [PMID: 8564842]
[77]
Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T. Tumour antigens recognized by T lymphocytes: At the core of cancer immunotherapy. Nat Rev Cancer 2014; 14(2): 135-46.
[http://dx.doi.org/10.1038/nrc3670] [PMID: 24457417]
[78]
Türeci Ö, Vormehr M, Diken M, Kreiter S, Huber C, Sahin U. Targeting the heterogeneity of cancer with individualized neoepitope vaccines. Clin Cancer Res 2016; 22(8): 1885-96.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1509] [PMID: 27084742]
[79]
Benteyn D, Heirman C, Bonehill A, Thielemans K, Breckpot K. mRNA-based dendritic cell vaccines. Expert Rev Vaccines 2015; 14(2): 161-76.
[http://dx.doi.org/10.1586/14760584.2014.957684] [PMID: 25196947]
[80]
Bonehill A, Tuyaerts S, Van Nuffel AM, et al. Enhancing the T-cell stimulatory capacity of human dendritic cells by co-electroporation with CD40L, CD70 and constitutively active TLR4 encoding mRNA. Mol Ther 2008; 16(6): 1170-80.
[http://dx.doi.org/10.1038/mt.2008.77] [PMID: 18431362]
[81]
Wilgenhof S, Van Nuffel AMT, Benteyn D, et al. A phase IB study on intravenous synthetic mRNA electroporated dendritic cell immunotherapy in pretreated advanced melanoma patients. Ann Oncol 2013; 24(10): 2686-93.
[http://dx.doi.org/10.1093/annonc/mdt245] [PMID: 23904461]
[82]
Wilgenhof S, Corthals J, Heirman C, et al. Phase II study of autologous monocyte-derived mrna electroporated dendritic cells (trimixdc-mel) plus ipilimumab in patients with pretreated advanced melanoma. J Clin Oncol 2016; 34(12): 1330-8.
[http://dx.doi.org/10.1200/JCO.2015.63.4121] [PMID: 26926680]
[83]
Amin A, Dudek AZ, Logan TF, et al. Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): Phase 2 study results. J Immunother Cancer 2015; 3: 14.
[http://dx.doi.org/10.1186/s40425-015-0055-3] [PMID: 25901286]
[84]
Sahin U, Derhovanessian E, Miller M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 2017; 547(7662): 222-6.
[http://dx.doi.org/10.1038/nature23003] [PMID: 28678784]
[85]
Selmi A, Vascotto F, Kautz-Neu K, et al. Uptake of synthetic naked RNA by skin-resident dendritic cells via macropinocytosis allows antigen expression and induction of T-cell responses in mice. Cancer Immunol Immunother 2016; 65(9): 1075-83.
[http://dx.doi.org/10.1007/s00262-016-1869-7] [PMID: 27422115]
[86]
Clausen BE, Stoitzner P. Functional specialization of skin dendritic cell subsets in regulating T cell responses. Front Immunol 2015; 6: 534.
[http://dx.doi.org/10.3389/fimmu.2015.00534] [PMID: 26557117]
[87]
Rauch S, Lutz J, Kowalczyk A, Schlake T, Heidenreich R. Rnactive(r) technology: Generation and testing of stable and immunogenic mRNA vaccines. Methods Mol Biol 2017; 1499: 89-107.
[http://dx.doi.org/10.1007/978-1-4939-6481-9_5] [PMID: 27987144]
[88]
Hong HS, Koch SD, Scheel B, et al. Distinct transcriptional changes in non-small cell lung cancer patients associated with multi-antigenic RNActive® CV9201 immunotherapy. Onco Immun 2016; 5(12)e1249560
[http://dx.doi.org/10.1080/2162402X.2016.1249560] [PMID: 28123889]
[89]
Zhou X, Li X, Wu M. miRNAs reshape immunity and inflammatory responses in bacterial infection. Signal Transduct Target Ther 2018; 3: 14.
[http://dx.doi.org/10.1038/s41392-018-0006-9] [PMID: 29844933]
[90]
Zhang C, Maruggi G, Shan H, Li J. Advances in mRNA vaccines for infectious diseases. Front Immunol 2019; 10: 594.
[http://dx.doi.org/10.3389/fimmu.2019.00594] [PMID: 30972078]
[91]
Jacobson JM, Routy JP, Welles S, et al. Dendritic cell immunotherapy for hiv-1 infection using autologous hiv-1 RNA: A randomized, double-blind, placebo-controlled clinical trial. J Acquir Immune Defic Syndr 2016; 72(1): 31-8.
[http://dx.doi.org/10.1097/QAI.0000000000000926] [PMID: 26751016]
[92]
Gay CL, DeBenedette MA, Tcherepanova IY, et al. Immunogenicity of AGS-004 dendritic cell therapy in patients treated during acute hiv infection. AIDS Res Hum Retroviruses 2018; 34(1): 111-22.
[http://dx.doi.org/10.1089/aid.2017.0071] [PMID: 28636433]
[93]
Alberer M, Gnad-Vogt U, Hong HS, et al. Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: An open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. Lancet 2017; 390(10101): 1511-20.
[http://dx.doi.org/10.1016/S0140-6736(17)31665-3] [PMID: 28754494]
[94]
Kallen KJ, Heidenreich R, Schnee M, et al. A novel, disruptive vaccination technology: self-adjuvanted RNActive® vaccines. Hum Vaccin Immunother 2013; 9(10): 2263-76.
[http://dx.doi.org/10.4161/hv.25181] [PMID: 23921513]
[95]
Bahl K, Senn JJ, Yuzhakov O, et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against h10n8 and h7n9 influenza viruses. Mol Ther 2017; 25(6): 1316-27.
[http://dx.doi.org/10.1016/j.ymthe.2017.03.035] [PMID: 28457665]
[96]
Jayasena SD. Aptamers: An emerging class of molecules that rival antibodies in diagnostics. Clin Chem 1999; 45(9): 1628-50.
[PMID: 10471678]
[97]
Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 1990; 249(4968): 505-10.
[http://dx.doi.org/10.1126/science.2200121] [PMID: 2200121]
[98]
Keefe AD, Pai S, Ellington A. Aptamers as therapeutics. Nat Rev Drug Discov 2010; 9(7): 537-50.
[http://dx.doi.org/10.1038/nrd3141] [PMID: 20592747]
[99]
Ismail SI, Alshaer W. Therapeutic aptamers in discovery, preclinical and clinical stages. Adv Drug Deliv Rev 2018; 134: 51-64.
[http://dx.doi.org/10.1016/j.addr.2018.08.006] [PMID: 30125605]
[100]
Vinores SA. Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine 2006; 1(3): 263-8.
[PMID: 17717967]
[101]
Adamis AP, Miller JW, Bernal MT, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994; 118(4): 445-50.
[http://dx.doi.org/10.1016/S0002-9394(14)75794-0] [PMID: 7943121]
[102]
Blaauwgeers HG, Holtkamp GM, Rutten H, et al. Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris. Evidence for a trophic paracrine relation. Am J Pathol 1999; 155(2): 421-8.
[http://dx.doi.org/10.1016/S0002-9440(10)65138-3] [PMID: 10433935]
[103]
Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994; 331(22): 1480-7.
[http://dx.doi.org/10.1056/NEJM199412013312203] [PMID: 7526212]
[104]
Drolet DW, Green LS, Gold L, Janjic N. Fit for the eye: Aptamers in ocular disorders. Nucleic Acid Ther 2016; 26(3): 127-46.
[http://dx.doi.org/10.1089/nat.2015.0573] [PMID: 26757406]
[105]
Gerard C, Gerard NP. C5A anaphylatoxin and its seven transmembrane-segment receptor. Annu Rev Immunol 1994; 12: 775-808.
[http://dx.doi.org/10.1146/annurev.iy.12.040194.004015] [PMID: 8011297]
[106]
Howard EL, Becker KCD, Rusconi CP, Becker RC. Factor IXa inhibitors as novel anticoagulants. Arterioscler Thromb Vasc Biol 2007; 27(4): 722-7.
[http://dx.doi.org/10.1161/01.ATV.0000259363.91070.f1] [PMID: 17272750]
[107]
Becker RC, Rusconi C, Sullenger B. Nucleic acid aptamers in therapeutic anticoagulation. Technology, development and clinical application. Thromb Haemost 2005; 93(6): 1014-20.
[http://dx.doi.org/10.1160/TH04-12-0790] [PMID: 15968382]
[108]
Vavalle JP, Cohen MG. The REG1 anticoagulation system: A novel actively controlled factor IX inhibitor using RNA aptamer technology for treatment of acute coronary syndrome. Future Cardiol 2012; 8(3): 371-82.
[http://dx.doi.org/10.2217/fca.12.5] [PMID: 22420328]
[109]
Cohen MG, Purdy DA, Rossi JS, et al. First clinical application of an actively reversible direct factor IXa inhibitor as an anticoagulation strategy in patients undergoing percutaneous coronary intervention. Circu 2010; 122(6): 614-22.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.927756] [PMID: 20660806]
[110]
Lincoff AM, Mehran R, Povsic TJ, et al. Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): A randomised clinical trial. Lancet 2016; 387(10016): 349-56.
[http://dx.doi.org/10.1016/S0140-6736(15)00515-2] [PMID: 26547100]
[111]
Zhou L-Y, He Z-Y, Xu T, Wei Y-Q. Current advances in small activating rnas for gene therapy: Principles, applications and challenges. Curr Gene Ther 2018; 18(3): 134-42.
[http://dx.doi.org/10.2174/1566523218666180619155018] [PMID: 29921205]
[112]
Li L-C, Okino ST, Zhao H, et al. Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci USA 2006; 103(46): 17337-42.
[http://dx.doi.org/10.1073/pnas.0607015103] [PMID: 17085592]
[113]
Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE, Corey DR. Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat Chem Biol 2007; 3(3): 166-73.
[http://dx.doi.org/10.1038/nchembio860] [PMID: 17259978]
[114]
Huang V, Qin Y, Wang J, et al. RNAa is conserved in mammalian cells. PLoS One 2010; 5(1)e8848
[http://dx.doi.org/10.1371/journal.pone.0008848] [PMID: 20107511]
[115]
Portnoy V, Lin SHS, Li KH, et al. saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription. Cell Res 2016; 26(3): 320-35.
[http://dx.doi.org/10.1038/cr.2016.22] [PMID: 26902284]
[116]
Kwok A, Raulf N, Habib N. Developing small activating RNA as a therapeutic: current challenges and promises. Ther Deliv 2019; 10(3): 151-64.
[http://dx.doi.org/10.4155/tde-2018-0061] [PMID: 30909853]
[117]
Yoon S, Rossi JJ. Therapeutic potential of small activating rnas (sarnas) in human cancers. Curr Pharm Biotechnol 2018; 19(8): 604-10.
[http://dx.doi.org/10.2174/1389201019666180528084059] [PMID: 29804529]
[118]
Setten RL, Lightfoot HL, Habib NA, Rossi JJ. Development of mtl-cebpa: Small activating rna drug for hepatocellular carcinoma. Curr Pharm Biotechnol 2018; 19(8): 611-21.
[http://dx.doi.org/10.2174/1389201019666180611093428] [PMID: 29886828]
[119]
Uppada V, Gokara M, Rasineni GK. Diagnosis and therapy with CRISPR advanced CRISPR based tools for point of care diagnostics and early therapies. Gene 2018; 656: 22-9.
[http://dx.doi.org/10.1016/j.gene.2018.02.066] [PMID: 29496558]
[120]
Blin K, Pedersen LE, Weber T, Lee SY. CRISPy-web: An online resource to design sgRNAs for CRISPR applications. Synth Syst Biotechnol 2016; 1(2): 118-21.
[http://dx.doi.org/10.1016/j.synbio.2016.01.003] [PMID: 29062934]
[121]
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Sci 2012; 337(6096): 816-21.
[http://dx.doi.org/10.1126/science.1225829] [PMID: 22745249]
[122]
Liu X, Homma A, Sayadi J, Yang S, Ohashi J, Takumi T. Sequence features associated with the cleavage efficiency of CRISPR/Cas9 system. Sci Rep 2016; 6: 19675.
[http://dx.doi.org/10.1038/srep19675] [PMID: 26813419]
[123]
Nowak CM, Lawson S, Zerez M, Bleris L. Guide RNA engineering for versatile Cas9 functionality. Nucl Acids Res 2016; 44(20): 9555-64.
[http://dx.doi.org/10.1093/nar/gkw908] [PMID: 27733506]
[124]
Kelley ML, Strezoska Ž, He K, Vermeulen A, Smith Av. Versatility of chemically synthesized guide RNAs for CRISPR-Cas9 genome editing. J Biotechnol 2016; 233: 74-83.
[http://dx.doi.org/10.1016/j.jbiotec.2016.06.011] [PMID: 27374403]
[125]
Bonetta L. RNA-based therapeutics: Ready for delivery. Cell 2009; 136(4): 581-4.
[http://dx.doi.org/10.1016/j.cell.2009.02.010] [PMID: 19239878]
[126]
He ZY, Zhang YG, Yang YH, et al. In vivo ovarian cancer gene therapy using crispr-cas9. Hum Gene Ther 2018; 29(2): 223-33.
[http://dx.doi.org/10.1089/hum.2017.209] [PMID: 29338433]
[127]
Fan P, He ZY, Xu T, et al. Exposing cancer with crispr-cas9: From genetic identification to clinical therapy. Transl Cancer Res 2018; 7(3): 817-27.
[http://dx.doi.org/10.21037/tcr.2018.06.16]
[128]
Cyranoski D. Chinese scientists to pioneer first human CRISPR trial. Nature 2016; 535(7613): 476-7.
[http://dx.doi.org/10.1038/nature.2016.20302] [PMID: 27466105]
[129]
He ZY, Men K, Qin Z, Yang Y, Xu T, Wei YQ. Non-viral and viral delivery systems for CRISPR-Cas9 technology in the biomedical field. Sci China Life Sci 2017; 60(5): 458-67.
[http://dx.doi.org/10.1007/s11427-017-9033-0] [PMID: 28527117]
[130]
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]
[131]
He ZY, Jin ZH, Zhan M, et al. Advances in quantum dot-mediated sirna delivery. Chin Chem Lett 2017; 28(9): 1851-6.
[http://dx.doi.org/10.1016/j.cclet.2017.07.012] [PMID: 24028896]
[132]
Zhang D, Lee H, Wang X, Rai A, Groot M, Jin Y. Exosome-mediated small rna delivery: A novel therapeutic approach for inflammatory lung responses. Mol Ther 2018; 26(9): 2119-30.
[http://dx.doi.org/10.1016/j.ymthe.2018.06.007] [PMID: 30005869]

Rights & Permissions Print Cite
Article Metrics
130
33
1
2
© 2024 Bentham Science Publishers | Privacy Policy