Challenges with the discovery of RNA-based therapeutics for flaviviruses

References

• Pierson TC, Diamond MS. The continued threat of emerging flaviviruses. Nat Microbiol. 2020;5(6):796–812.
   PubMed Web of Science ®Google Scholar
• Pierson TC, Diamond MS. The emergence of Zika virus and its new clinical syndromes. Nature. 2018;560:573–581.
   PubMed Web of Science ®Google Scholar
• Zhao R, Wang M, Cao J, et al. Flavivirus: from structure to therapeutics development. Life (Basel). 2021;11:615.
   PubMedGoogle Scholar
• Blahove MR, Carter JR. Flavivirus persistence in wildlife populations. Viruses. 2021;13:2099.
   PubMedGoogle Scholar
• Tompa DR, Immanuel A, Srikanth S, et al. Trends and strategies to combat viral infections: a review on FDA approved antiviral drugs. Int j biol macromol. 2021;172:524–541.
   PubMed Web of Science ®Google Scholar
• Kausar S, Said Khan F, Ishaq Mujeeb Ur Rehman M, et al. A review: mechanism of action of antiviral drugs. Int J Immunopathol Pharmacol. 2021;35:20587384211002621.
   Google Scholar
• Damase TR, Sukhovershin R, Boada C, et al. The limitless future of RNA therapeutics. Front Bioeng Biotechnol. 2021;9:628137.
   PubMed Web of Science ®Google Scholar
• Meganck RM, Baric RS Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases. Nat Med 2021;27:401–410. 3 10.1038/s41591-021-01282-0
   PubMed Web of Science ®Google Scholar
• Kaczmarek JC, Kowalski PS, Anderson DG. Advances in the delivery of RNA therapeutics: from concept to clinical reality. Genome Med. 2017;9(1):60.
   PubMed Web of Science ®Google Scholar
• Winkle M, El-Daly SM, Fabbri M, et al. Noncoding RNA therapeutics — challenges and potential solutions. Nat Rev Drug Discov 2021;20:629–651. 8 10.1038/s41573-021-00219-z
   PubMed Web of Science ®Google Scholar
• Anderson KP, Fox MC, Brown-Driver V, et al. Inhibition of human cytomegalovirus immediate-early gene expression by an antisense oligonucleotide complementary to immediate-early RNA. Antimicrob Agents Chemother. 1996;40(9):2004–2011. DOI:10.1128/AAC.40.9.2004
   PubMed Web of Science ®Google Scholar
• Hua Y, Sahashi K, Hung G, et al. Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev. 2010;24(15):1634–1644. DOI:10.1101/gad.1941310
   PubMed Web of Science ®Google Scholar
• Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010;327:198–201.
   PubMed Web of Science ®Google Scholar
• Zhang L, Li Q, Ding X, et al. Antisense oligonucleotides targeting raf-1 block Japanese encephalitis virus in vitro and in vivo. Nucleic Acid Ther. 2017;27(2):78–86. DOI:10.1089/nat.2016.0626
   PubMedGoogle Scholar
• Phumesin P, Junking M, Panya A, et al. Vivo-morpholino oligomers strongly inhibit dengue virus replication and production. Arch Virol. 2018;163(4):867–876. DOI:10.1007/s00705-017-3666-9
   PubMedGoogle Scholar
• Jellinek D, Green LS, Bell C, et al. Inhibition of receptor binding by high-affinity RNA ligands to vascular endothelial growth factor. Biochemistry. 1994;33:10450–10456.
   PubMed Web of Science ®Google Scholar
• Jung JI, Han SR, Lee SW. Development of RNA aptamer that inhibits methyltransferase activity of dengue virus. Biotechnol Lett. 2018;40(2):315–324.
   PubMedGoogle Scholar
• Han SR, Lee SW. Inhibition of Japanese encephalitis virus (JEV) replication by specific RNA aptamer against JEV methyltransferase. Biochem Biophys Res Commun. 2017;483(1):687–693.
   PubMedGoogle Scholar
• Falk SP, Weisblum B. Aptamer displacement screen for flaviviral RNA methyltransferase inhibitors. J Biomol Screen. 2014;19(8):1147–1153.
   PubMedGoogle Scholar
• Mello CC, Conte D Jr. Revealing the world of RNA interference. Nature. 2004;431:338–342.
   PubMed Web of Science ®Google Scholar
• Haasnoot J, Westerhout EM, Berkhout B RNA interference against viruses: strike and counterstrike. Nat Biotechnol 2007;25:1435–1443. 12 10.1038/nbt1369
   PubMed Web of Science ®Google Scholar
• Lee HY, Zhou K, Smith AM, et al. Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing. Nucleic Acids Res. 2013;41(13):6568–6576. DOI:10.1093/nar/gkt361
   PubMed Web of Science ®Google Scholar
• Bernstein E, Caudy AA, Hammond SM, et al. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001;409:363–366.
   PubMed Web of Science ®Google Scholar
• Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001;411:494–498.
   PubMed Web of Science ®Google Scholar
• Caplen NJ, Parrish S, Imani F, et al. Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems. Proc Natl Acad Sci U S A. 2001;98(17):9742–9747. DOI:10.1073/pnas.171251798
   PubMed Web of Science ®Google Scholar
• Bai F, Wang T, Pal U, et al. Use of RNA interference to prevent lethal murine west nile virus infection. J Infect Dis. 2005;191(7):1148–1154. DOI:10.1086/428507
   PubMedGoogle Scholar
• Beloor J, Maes N, Ullah I, et al. Small interfering RNA-Mediated control of virus replication in the CNS is therapeutic and enables natural immunity to west nile virus. Cell Host Microbe 2018;23:549–56.e3. 4 10.1016/j.chom.2018.03.001
   PubMed Web of Science ®Google Scholar
• Zhang R, Fu Y, Cheng M, et al. sEvsrvg selectively delivers antiviral siRNA to fetus brain, inhibits ZIKV infection and mitigates ZIKV-induced microcephaly in mouse model. Mol Ther 2022;30:2078–2091. 5 10.1016/j.ymthe.2021.10.009
   PubMed Web of Science ®Google Scholar
• Giulietti M, Righetti A, Cianfruglia L, et al. To accelerate the Zika beat: candidate design for RNA interference-based therapy. Virus Res. 2018;255:133–140.
   PubMed Web of Science ®Google Scholar
• Perez-Mendez M, Zárate-Segura P, Salas-Benito J, et al. Sirna design to silence the 3‘UTR Region of Zika Virus. BioMed Res Int. 2020;2020:6759346.
   PubMedGoogle Scholar
• Ong SP, Choo BG, Chu JJ, et al. Expression of vector-based small interfering RNA against West Nile virus effectively inhibits virus replication. Antiviral Res. 2006;72(3):216–223. DOI:10.1016/j.antiviral.2006.06.005
   PubMedGoogle Scholar
• Korrapati AB, Swaminathan G, Singh A, et al. Adenovirus Delivered Short Hairpin RNA targeting a conserved site in the 5′ non-translated region inhibits all four serotypes of dengue viruses. PLoS Negl Trop Dis. 2012;6(7):e1735. DOI:10.1371/journal.pntd.0001735
   PubMedGoogle Scholar
• Karothia D, Kumar Dash P, Parida M, et al. Vector derived artificial miRNA mediated inhibition of West Nile virus replication and protein expression. Gene. 2020;729:144300.
   PubMedGoogle Scholar
• Pacca CC, Severino AA, Mondini A, et al. RNA interference inhibits yellow fever virus replication in vitro and in vivo. Virus Genes. 2009;38:224–231.
   PubMed Web of Science ®Google Scholar
• Karothia D, Dash PK, Parida M, et al. Inhibition of west nile virus replication by bifunctional sirna targeting the NS2A and NS5 conserved region. Curr Gene Ther 2018;18:180–190. 3 10.2174/1566523218666180607091311
   PubMedGoogle Scholar
• Nawtaisong P, Keith J, Fraser T, et al. Effective suppression of Dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome. Virol J. 2009;6(1):73. DOI:10.1186/1743-422X-6-73
   PubMedGoogle Scholar
• Carter JR, Keith JH, Barde PV, et al. Targeting of highly conserved Dengue virus sequences with anti-Dengue virus trans-splicing group I introns. BMC Mol Biol. 2010;11(1):84. DOI:10.1186/1471-2199-11-84
   PubMedGoogle Scholar
• Soucek L, Whitfield JR, Sodir NM, et al. Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice. Genes Dev. 2013;27(5):504–513. DOI:10.1101/gad.205542.112
   PubMed Web of Science ®Google Scholar
• Janas MM, Schlegel MK, Harbison CE, et al. Selection of GalNAc-conjugated siRnas with limited off-target-driven rat hepatotoxicity. Nat Commun. 2018;9(1):723. DOI:10.1038/s41467-018-02989-4
   PubMedGoogle Scholar
• Setten RL, Rossi JJ, Han SP The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov 2019;18:421–446. 6 10.1038/s41573-019-0017-4
   PubMed Web of Science ®Google Scholar
• Canton I, Battaglia G. Endocytosis at the nanoscale. Chem Soc Rev. 2012;41(7):2718–2739.
   PubMed Web of Science ®Google Scholar
• Gilleron J, Querbes W, Zeigerer A, et al. Image-based analysis of lipid nanoparticle–mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat Biotechnol. 2013;31(7):638–646. DOI:10.1038/nbt.2612
   PubMed Web of Science ®Google Scholar
• Lönn P, Kacsinta AD, Cui XS, et al. Enhancing endosomal escape for intracellular delivery of macromolecular biologic therapeutics. Sci Rep. 2016;6(1):32301. DOI:10.1038/srep32301
   PubMed Web of Science ®Google Scholar
• Wittrup A, Ai A, Liu X, et al. Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown. Nat Biotechnol. 2015;33(8):870–876. DOI:10.1038/nbt.3298
   PubMed Web of Science ®Google Scholar
• Sahay G, Querbes W, Alabi C, et al. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat Biotechnol. 2013;31(7):653–658. DOI:10.1038/nbt.2614
   PubMed Web of Science ®Google Scholar
• Barouch-Bentov R, Einav S. Turning up your nose for a flaviviral encephalitis cure. Cell Host Microbe. 2018;23(4):427–429.
   PubMedGoogle Scholar
• Zimmermann TS, Lee AC, Akinc A, et al. Rnai-mediated gene silencing in non-human primates. Nature. 2006;441(7089):111–114. DOI:10.1038/nature04688
   PubMed Web of Science ®Google Scholar
• Nakamura Y, Kogure K, Futaki S, et al. Octaarginine-modified multifunctional envelope-type nano device for siRNA. J Control Release. 2007;119:360–367.
   PubMed Web of Science ®Google Scholar
• Akita H, Noguchi Y, Hatakeyama H, et al. Molecular tuning of a vitamin E-Scaffold pH-Sensitive and reductive cleavable lipid-like material for accelerated in vivo hepatic siRNA Delivery. ACS Biomater Sci Eng. 2015;1(9):834–844. DOI:10.1021/acsbiomaterials.5b00203
   PubMedGoogle Scholar
• Akinc A, Zumbuehl A, Goldberg M, et al. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat Biotechnol. 2008;26(5):561–569. DOI:10.1038/nbt1402
   PubMed Web of Science ®Google Scholar
• Martins S, Costa-Lima S, Carneiro T, et al. Solid lipid nanoparticles as intracellular drug transporters: an investigation of the uptake mechanism and pathway. Int J Pharm. 2012;430(1–2):216–227. DOI:10.1016/j.ijpharm.2012.03.032
   PubMedGoogle Scholar
• Alvarez-Erviti L, Seow Y, Yin H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29(4):341–345. DOI:10.1038/nbt.1807
   PubMed Web of Science ®Google Scholar
• Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1. N Engl J Med. 2021;384(13):1216–1226. DOI:10.1056/NEJMoa2021712
   PubMed Web of Science ®Google Scholar
• Adams D, Gonzalez-Duarte A, O’riordan WD, et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018;379(1):11–21. DOI:10.1056/NEJMoa1716153
   PubMed Web of Science ®Google Scholar
• Suhr OB, Coelho T, Buades J, et al. Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J Rare Dis. 2015;10(1):109. DOI:10.1186/s13023-015-0326-6
   PubMed Web of Science ®Google Scholar
• Ma D, Tian S, Baryza J, et al. Reductively Responsive Hydrogel Nanoparticles with Uniform Size, Shape, and Tunable Composition for Systemic siRNA Delivery in vivo. Mol Pharm. 2015;12(10):3518–3526. DOI:10.1021/acs.molpharmaceut.5b00054
   PubMedGoogle Scholar
• Ray RM, Hansen AH, Taskova M, et al. Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides. Beilstein J Org Chem. 2021;17:891–907.
   PubMedGoogle Scholar
• Torrecilla J, Del Pozo-Rodríguez A, Apaolaza PS, et al. Solid lipid nanoparticles as non-viral vector for the treatment of chronic hepatitis C by RNA interference. Int J Pharm. 2015;479(1):181–188. DOI:10.1016/j.ijpharm.2014.12.047
   PubMedGoogle Scholar
• Tao W, Davide JP, Cai M, et al. Noninvasive imaging of lipid nanoparticle-mediated systemic delivery of small-interfering RNA to the liver. Mol Ther. 2010;18:1657–1666.
   PubMed Web of Science ®Google Scholar
• Zhang C, Ren W, Liu Q, et al. Transportan-derived cell-penetrating peptide delivers siRNA to inhibit replication of influenza virus in vivo. Drug Des Devel Ther. 2019;13:1059–1068.
   PubMed Web of Science ®Google Scholar
• Kulkarni JA, Darjuan MM, Mercer JE, et al. On the Formation and Morphology of Lipid Nanoparticles Containing Ionizable Cationic Lipids and siRNA. ACS Nano. 2018;12:4787–4795.
   PubMed Web of Science ®Google Scholar
• Semple SC, Akinc A, Chen J, et al. Rational design of cationic lipids for siRNA delivery. Nat Biotechnol. 2010;28:172–176.
   PubMed Web of Science ®Google Scholar
• Jayaraman M, Ansell SM, Mui BL, et al. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew Chem Int Ed Engl. 2012;51:8529–8533.
   PubMed Web of Science ®Google Scholar
• Ly S, Navaroli DM, Didiot MC, et al. Visualization of self-delivering hydrophobically modified siRNA cellular internalization. Nucleic Acids Res. 2017;45(1):15–25. DOI:10.1093/nar/gkw1005
   PubMedGoogle Scholar
• Belliveau NM, Huft J, Lin PJ, et al. Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for in vivo Delivery of siRNA. Mol Ther Nucleic Acids. 2012;1:e37.
   PubMedGoogle Scholar
• Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol. 2011;30(1):16–34.
   PubMed Web of Science ®Google Scholar
• Sledz CA, Holko M, de Veer MJ, et al. Activation of the interferon system by short-interfering RNAs. Nat Cell Biol. 2003;5(9):834–839. DOI:10.1038/ncb1038
   PubMed Web of Science ®Google Scholar
• 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):1222–1230.
   PubMed Web of Science ®Google Scholar
• 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):1002–1007. DOI:10.1038/nbt1122
   PubMed Web of Science ®Google Scholar
• Judge AD, Bola G, Lee AC, et al. Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol Ther. 2006;13(3):494–505. DOI:10.1016/j.ymthe.2005.11.002
   PubMed Web of Science ®Google Scholar
• Mendell JR, Rodino-Klapac LR, Sahenk Z, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013;74(5):637–647. DOI:10.1002/ana.23982
   PubMed Web of Science ®Google Scholar
• Cirak S, Arechavala-Gomeza V, Guglieri M, et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet. 2011;378(9791):595–605. DOI:10.1016/S0140-6736(11)60756-3
   PubMed Web of Science ®Google Scholar
• Hong DS, Kang YK, Borad M, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br J Cancer. 2020;122(11):1630–1637. DOI:10.1038/s41416-020-0802-1
   PubMed Web of Science ®Google Scholar
• Wu Q, Wang X, Ding SW. Viral suppressors of RNA-based viral immunity: host targets. Cell Host Microbe. 2010;8(1):12–15.
   PubMed Web of Science ®Google Scholar
• Li F, Ding SW. Virus counterdefense: diverse strategies for evading the RNA-silencing immunity. Annu Rev Microbiol. 2006;60(1):503–531.
   PubMedGoogle Scholar
• Schnettler E, Sterken MG, Leung JY, et al. Noncoding flavivirus RNA displays RNA interference suppressor activity in insect and Mammalian cells. J Virol. 2012;86(24):13486–13500. DOI:10.1128/JVI.01104-12
   PubMed Web of Science ®Google Scholar
• Kakumani PK, Ponia SS, Rk S, et al. Role of RNA interference (RNAi) in dengue virus replication and identification of NS4B as an RNAi suppressor. J Virol. 2013;87(16):8870–8883. DOI:10.1128/JVI.02774-12
   PubMed Web of Science ®Google Scholar
• Samuel GH, Wiley MR, Badawi A, et al. Yellow fever virus capsid protein is a potent suppressor of RNA silencing that binds double-stranded RNA. Proc Natl Acad Sci U S A. 2016;113(48):13863–13868. DOI:10.1073/pnas.1600544113
   PubMed Web of Science ®Google Scholar
• Kakumani PK, Rajgokul KS, Ponia SS, et al. Dengue NS3, an RNAi suppressor, modulates the human miRNA pathways through its interacting partner. Biochem J. 2015;471(1):89–99. DOI:10.1042/BJ20150445
   PubMedGoogle Scholar
• Funk A, Truong K, Nagasaki T, et al. RNA structures required for production of subgenomic flavivirus RNA. J Virol. 2010;84(21):11407–11417. DOI:10.1128/JVI.01159-10
   PubMed Web of Science ®Google Scholar
• Lin KC, Chang HL, Chang RY. Accumulation of a 3′-Terminal Genome Fragment in Japanese Encephalitis Virus-Infected Mammalian and Mosquito Cells. J Virol. 2004;78(10):5133–5138.
   PubMed Web of Science ®Google Scholar
• Pijlman GP, Funk A, Kondratieva N, et al. A highly structured, nuclease-resistant, noncoding RNA produced by flaviviruses is required for pathogenicity. Cell Host Microbe. 2008;4(6):579–591. DOI:10.1016/j.chom.2008.10.007
   PubMed Web of Science ®Google Scholar
• Schuessler A, Funk A, Lazear HM, et al. West Nile virus noncoding subgenomic RNA contributes to viral evasion of the type I interferon-mediated antiviral response. J Virol. 2012;86(10):5708–5718. DOI:10.1128/JVI.00207-12
   PubMed Web of Science ®Google Scholar
• Muñoz-Jordan JL, Sánchez-Burgos GG, Laurent-Rolle M, et al. Inhibition of interferon signaling by dengue virus. Proc Natl Acad Sci U S A. 2003;100(24):14333–14338. DOI:10.1073/pnas.2335168100
   PubMed Web of Science ®Google Scholar
• Qiu Y, Xu YP, Wang M, et al. Flavivirus induces and antagonizes antiviral RNA interference in both mammals and mosquitoes. Sci Adv 2020;6:eaax7989. 6 10.1126/sciadv.aax7989
   PubMed Web of Science ®Google Scholar
• Hu WY, Myers CP, Kilzer JM, et al. Inhibition of retroviral pathogenesis by RNA interference. Curr Biol. 2002;12(15):1301–1311. DOI:10.1016/S0960-9822(02)00975-2
   PubMedGoogle Scholar
• Westerhout EM, Ter Brake O, Berkhout B. The virion-associated incoming HIV-1 RNA genome is not targeted by RNA interference. Retrovirology. 2006;3:57.
   PubMed Web of Science ®Google Scholar
• Geiss BJ, Pierson TC, Diamond MS. Actively replicating West Nile virus is resistant to cytoplasmic delivery of siRNA. Virol J. 2005;2(1):53.
   PubMedGoogle Scholar
• Matzen K, Elzaouk L, Matskevich AA, et al. Rnase H-mediated retrovirus destruction in vivo triggered by oligodeoxynucleotides. Nat Biotechnol. 2007;25(6):669–674. DOI:10.1038/nbt1311
   PubMedGoogle Scholar
• Gitlin L, Stone JK, Andino R. Poliovirus escape from RNA interference: short interfering RNA-target recognition and implications for therapeutic approaches. J Virol. 2005;79:1027–1035.
   PubMed Web of Science ®Google Scholar
• Westerhout EM, Ooms M, Vink M, et al. HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome. Nucleic Acids Res. 2005;33(2):796–804. DOI:10.1093/nar/gki220
   PubMedGoogle Scholar
• Boden D, Pusch O, Lee F, et al. Human immunodeficiency virus type 1 escape from RNA interference. J Virol. 2003;77(21):11531–11535. DOI:10.1128/JVI.77.21.11531-11535.2003
   PubMed Web of Science ®Google Scholar
• Wu Z, Xue Y, Wang B, et al. Broad-spectrum antiviral activity of RNA interference against four genotypes of Japanese encephalitis virus based on single microRNA polycistrons. PLoS ONE. 2011;6:e26304.
   PubMed Web of Science ®Google Scholar
• Xie PW, Xie Y, Zhang XJ, et al. Inhibition of Dengue virus 2 replication by artificial micrornas targeting the conserved regions. Nucleic Acid Ther. 2013;23(4):244–252. DOI:10.1089/nat.2012.0405
   PubMedGoogle Scholar
• Gubler DJ. Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol. 2002;10(2):100–103.
   PubMedGoogle Scholar
• Kauffman EB, Kramer LD. Zika Virus Mosquito Vectors: competence, Biology, and Vector Control. J Infect Dis. 2017;216(suppl_10):S976–s90.
   PubMedGoogle Scholar
• Monath TP, Vasconcelos PF. Yellow fever. J Clin Virol. 2015;64:160–173.
   PubMed Web of Science ®Google Scholar
• Ball RL, Bajaj P, Whitehead KA. Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization. Int J Nanomedicine. 2017;12:305–315.
   PubMed Web of Science ®Google Scholar
• Shirane D, Tanaka H, Nakai Y, et al. Development of an Alcohol Dilution–Lyophilization Method for Preparing Lipid Nanoparticles Containing Encapsulated siRNA. Biol Pharm Bull. 2018;41(8):1291–1294. DOI:10.1248/bpb.b18-00208
   PubMed Web of Science ®Google Scholar
• Muramatsu H, Lam K, Bajusz C, et al. Lyophilization provides long-term stability for a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine. Mol Ther. 2022;30(5):1941–1951. DOI:10.1016/j.ymthe.2022.02.001
   PubMed Web of Science ®Google Scholar
• Paunovska K, Loughrey D, Dahlman JE. Drug delivery systems for RNA therapeutics. Nat Rev Genet. 2022;23(5):1–16.
   PubMedGoogle Scholar
• Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017;377(18):1723–1732. DOI:10.1056/NEJMoa1702752
   PubMed Web of Science ®Google Scholar
• Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. N Engl J Med. 2018;378(7):625–635. DOI:10.1056/NEJMoa1710504
   PubMed Web of Science ®Google Scholar
• Charleston JS, Schnell FJ, Dworzak J, et al. Eteplirsen treatment for Duchenne muscular dystrophy: exon skipping and dystrophin production. Neurology. 2018;90:e2146–54.
   PubMed Web of Science ®Google Scholar
• Cui L, Pereira S, Sonzini S, et al. Development of a high-throughput platform for screening lipid nanoparticles for mRNA delivery. Nanoscale. 2022;14:1480–1491.
   PubMed Web of Science ®Google Scholar
• Abbott TR, Dhamdhere G, Liu Y, et al. Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza. Cell. 2020;181(4):865–76.e12. DOI:10.1016/j.cell.2020.04.020
   PubMed Web of Science ®Google Scholar
• Camacho C, Coulouris G, Avagyan V, et al. BLAST+: architecture and applications. BMC Bioinf. 2009;10:421.
   PubMed Web of Science ®Google Scholar
• Fakhr E, Zare F, Teimoori-Toolabi L. Precise and efficient siRNA design: a key point in competent gene silencing. Cancer Gene Ther. 2016;23(4):73–82.
   PubMed Web of Science ®Google Scholar
• Zhou Z, Kennell C, Lee JY, et al. Calcium phosphate-polymer hybrid nanoparticles for enhanced triple negative breast cancer treatment via co-delivery of paclitaxel and miR-221/222 inhibitors. Nanomedicine. 2017;13(2):403–410. DOI:10.1016/j.nano.2016.07.016
   PubMed Web of Science ®Google Scholar
• Nair JK, Attarwala H, Sehgal A, et al. Impact of enhanced metabolic stability on pharmacokinetics and pharmacodynamics of GalNAc–siRNA conjugates. Nucleic Acids Res. 2017;45(19):10969–10977. DOI:10.1093/nar/gkx818
   PubMed Web of Science ®Google Scholar
• Ahn DG, Lee W, Choi JK, et al. Interference of ribosomal frameshifting by antisense peptide nucleic acids suppresses SARS coronavirus replication. Antiviral Res. 2011;91(1):1–10. DOI:10.1016/j.antiviral.2011.04.009
   PubMed Web of Science ®Google Scholar
• Zhou J, Lazar D, Li H, et al. Receptor-targeted aptamer-siRNA conjugate-directed transcriptional regulation of HIV-1. Theranostics. 2018;8:1575–1590.
   PubMedGoogle Scholar
• Sugo T, Terada M, Oikawa T, et al. Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles. J Control Release. 2016;237:1–13.
   PubMed Web of Science ®Google Scholar
• Modhiran N, Song H, Liu L, et al. A broadly protective antibody that targets the flavivirus NS1 protein. Science. 2021;371:190–194.
   PubMedGoogle Scholar
• Miller JL, Lachica R, Sayce AC, et al. Liposome-mediated delivery of iminosugars enhances efficacy against dengue virus in vivo. Antimicrob Agents Chemother. 2012;56(12):6379–6386. DOI:10.1128/AAC.01554-12
   PubMedGoogle Scholar
• Liu Y, Wang X, Li J, et al. Sphingosine 1-Phosphate Liposomes for Targeted Nitric Oxide Delivery to Mediate Anticancer Effects against Brain Glioma Tumors. Adv Mater. 2021;33(30):e2101701. DOI:10.1002/adma.202101701
   PubMedGoogle Scholar
• Ding Y, Jiang Z, Saha K, et al. Gold nanoparticles for nucleic acid delivery. Mol Ther. 2014;22(6):1075–1083. DOI:10.1038/mt.2014.30
   PubMed Web of Science ®Google Scholar
• Komatsu Y, Tanaka C, Komorizono R, et al. In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector. Sci Rep. 2020;10(1):5890. DOI:10.1038/s41598-020-62630-7
   PubMedGoogle Scholar
• Yeung JC, Wagnetz D, Cypel M, et al. Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig. Mol Ther. 2012;20(6):1204–1211. DOI:10.1038/mt.2012.57
   PubMedGoogle Scholar
• Suzuki Y, Hyodo K, Suzuki T, et al. Biodegradable lipid nanoparticles induce a prolonged RNA interference-mediated protein knockdown and show rapid hepatic clearance in mice and nonhuman primates. Int J Pharm. 2017;519(1–2):34–43. DOI:10.1016/j.ijpharm.2017.01.016
   PubMedGoogle Scholar
• Nguyen K, Dang PN, Alsberg E. Functionalized, biodegradable hydrogels for control over sustained and localized siRNA delivery to incorporated and surrounding cells. Acta Biomater. 2013;9(1):4487–4495.
   PubMed Web of Science ®Google Scholar
• Borgheti-Cardoso LN, Kooijmans SAA, Fens M, et al. In Situ Gelling Liquid Crystalline System as Local siRNA Delivery System. Mol Pharm. 2017;14(5):1681–1690. DOI:10.1021/acs.molpharmaceut.6b01141
   PubMedGoogle Scholar
• Wang LL, Chung JJ, Li EC, et al. Injectable and protease-degradable hydrogel for siRNA sequestration and triggered delivery to the heart. J Control Release. 2018;285:152–161.
   PubMed Web of Science ®Google Scholar
• Castleberry SA, Almquist BD, Li W, et al. Self-Assembled Wound Dressings Silence MMP-9 and Improve Diabetic Wound Healing in vivo. Adv Mater. 2016;28(9):1809–1817. DOI:10.1002/adma.201503565
   PubMed Web of Science ®Google Scholar
• Castleberry SA, Golberg A, Sharkh MA, et al. Nanolayered siRNA delivery platforms for local silencing of CTGF reduce cutaneous scar contraction in third-degree burns. Biomaterials. 2016;95:22–34.
   PubMedGoogle Scholar
• Benam KH, Dauth S, Hassell B, et al. Engineered in vitro disease models. Annu Rev Pathol. 2015;10(1):195–262. DOI:10.1146/annurev-pathol-012414-040418
   PubMed Web of Science ®Google Scholar
• Lancaster MA, Knoblich JA. Organogenesis in a dish: modeling development and disease using organoid technologies. Science. 2014;345:1247125.
   PubMed Web of Science ®Google Scholar
• Reynolds A, Leake D, Boese Q, et al. Rational siRNA design for RNA interference. Nat Biotechnol. 2004;22(3):326–330. DOI:10.1038/nbt936
   PubMed Web of Science ®Google Scholar
• Zimmermann TS, Karsten V, Chan A, et al. Clinical Proof of Concept for a Novel Hepatocyte-Targeting GalNAc-siRNA Conjugate. Mol Ther. 2017;25(1):71–78. DOI:10.1016/j.ymthe.2016.10.019
   PubMed Web of Science ®Google Scholar
• DeVincenzo J, Lambkin-Williams R, Wilkinson T, et al. A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Proc Natl Acad Sci U S A. 2010;107(19):8800–8805. DOI:10.1073/pnas.0912186107
   PubMed Web of Science ®Google Scholar
• Kleinman ME, Yamada K, Takeda A, et al. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature. 2008;452:591–597.
   PubMed Web of Science ®Google Scholar
• Djupesland PG, Skretting A, Winderen M, et al. Breath actuated device improves delivery to target sites beyond the nasal valve. Laryngoscope. 2006;116(3):466–472. DOI:10.1097/01.MLG.0000199741.08517.99
   PubMed Web of Science ®Google Scholar
• Miyake MM, Bleier BS. The blood-brain barrier and nasal drug delivery to the central nervous system. Am J Rhinol Allergy. 2015;29(2):124–127.
   PubMed Web of Science ®Google Scholar
• Ter Brake O, Konstantinova P, Ceylan M, et al. Silencing of HIV-1 with RNA interference: a multiple shRNA approach. Mol Ther. 2006;14(6):883–892. DOI:10.1016/j.ymthe.2006.07.007
   PubMedGoogle Scholar
• Bullard-Feibelman KM, Govero J, Zhu Z, et al. The FDA-approved drug sofosbuvir inhibits Zika virus infection. Antiviral Res. 2017;137:134–140.
   PubMed Web of Science ®Google Scholar
• Julander JG, Siddharthan V, Evans J, et al. Efficacy of the broad-spectrum antiviral compound BCX4430 against Zika virus in cell culture and in a mouse model. Antiviral Res. 2017;137:14–22.
   PubMed Web of Science ®Google Scholar
• Felicetti T, Burali MS, Gwee CP, et al. Sustainable, three-component, one-pot procedure to obtain active anti-flavivirus agents. Eur J Med Chem. 2021;210:112992.
   PubMedGoogle Scholar
• Felicetti T, Manfroni G, Cecchetti V, et al. Broad-Spectrum Flavivirus Inhibitors: a Medicinal Chemistry Point of View. ChemMedchem. 2020;15:2391–2419.
   PubMedGoogle Scholar
• Cannalire R, Ki Chan KW, Burali MS, et al. Pyridobenzothiazolones Exert Potent Anti-Dengue Activity by Hampering Multiple Functions of NS5 Polymerase. ACS Med Chem Lett. 2020;11(5):773–782. DOI:10.1021/acsmedchemlett.9b00619
   PubMedGoogle Scholar
• Yuan S, Chan JF, den-Haan H, et al. Structure-based discovery of clinically approved drugs as Zika virus NS2B-NS3 protease inhibitors that potently inhibit Zika virus infection in vitro and in vivo. Antiviral Res. 2017;145:33–43.
   PubMed Web of Science ®Google Scholar
• Li Z, Brecher M, Deng YQ, et al. Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction. Cell Res. 2017;27:1046–1064.
   PubMed Web of Science ®Google Scholar
• Luo D, Vasudevan SG, Lescar J. The flavivirus NS2B-NS3 protease-helicase as a target for antiviral drug development. Antiviral Res. 2015;118:148–158.
   PubMed Web of Science ®Google Scholar
• Poh MK, Yip A, Zhang S, et al. A small molecule fusion inhibitor of dengue virus. Antiviral Res. 2009;84(3):260–266. DOI:10.1016/j.antiviral.2009.09.011
   PubMed Web of Science ®Google Scholar
• Schmidt AG, Lee K, Yang PL, et al. Small-molecule inhibitors of dengue-virus entry. PLOS Pathog. 2012;8(4):e1002627. DOI:10.1371/journal.ppat.1002627
   PubMed Web of Science ®Google Scholar
• Byrd CM, Dai D, Grosenbach DW, et al. A novel inhibitor of dengue virus replication that targets the capsid protein. Antimicrob Agents Chemother. 2013;57(1):15–25. DOI:10.1128/AAC.01429-12
   PubMed Web of Science ®Google Scholar
• Scaturro P, Trist IM, Paul D, et al. Characterization of the mode of action of a potent dengue virus capsid inhibitor. J Virol. 2014;88(19):11540–11555. DOI:10.1128/JVI.01745-14
   PubMed Web of Science ®Google Scholar
• Smith JL, Sheridan K, Parkins CJ, et al. Characterization and structure-activity relationship analysis of a class of antiviral compounds that directly bind dengue virus capsid protein and are incorporated into virions. Antiviral Res. 2018;155:12–19.
   PubMedGoogle Scholar
• Kaptein SJF, Goethals O, Kiemel D, et al. A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction. Nature. 2021;598(7881):504–509. DOI:10.1038/s41586-021-03990-6
   PubMed Web of Science ®Google Scholar
• Lyu B, Wang C, Bie Y, et al. Enoxacin Shows Broad-Spectrum Antiviral Activity against Diverse Viruses by Enhancing Antiviral RNA Interference in Insects. J Virol 2022;96:e0177821. 4 10.1128/jvi.01778-21
   PubMedGoogle Scholar
• Lee E, Bujalowski PJ, Teramoto T, et al. Structures of flavivirus RNA promoters suggest two binding modes with NS5 polymerase. Nat Commun. 2021;12(1):2530. DOI:10.1038/s41467-021-22846-1
   PubMed Web of Science ®Google Scholar
• Ooi YS, Majzoub K, Flynn RA, et al. An RNA-centric dissection of host complexes controlling flavivirus infection. Nat Microbiol. 2019;4(12):2369–2382. DOI:10.1038/s41564-019-0518-2
   PubMed Web of Science ®Google Scholar
• Hoffmann HH, Schneider WM, Rozen-Gagnon K, et al. TMEM41B is a Pan-flavivirus Host Factor. Cell. 2021;184(1):133–48.e20. DOI:10.1016/j.cell.2020.12.005
   PubMed Web of Science ®Google Scholar