Latest Development on RNA-Based Drugs and Vaccines

References

• Drews J. Drug discovery: a historical perspective. Science 291, 1960–1964 (2000).
   Google Scholar
• Dimitrov DS. Therapeutic proteins. Methods Mol. Biol. 899, 1–26 (2012).
   PubMedGoogle Scholar
• Chen J, Xie J. Progress on RNAi-based molecular medicines. Int. J. Nanomed. 7, 3971–3980 (2012).
   PubMed Web of Science ®Google Scholar
• Brawerman G. Eukaryotic messenger RNA. Annu. Rev. Biochem. 43, 621–642 (1974).
   PubMed Web of Science ®Google Scholar
• Burgess DJ. RNA stability: remember your driver. Nat. Rev. Genet. 13, 72 (2012).
   PubMed Web of Science ®Google Scholar
• Perche F, Torchilin VP. Recent trends in multifunctional liposomal nanocarriers for enhanced tumor targeting. J. Drug Deliv. 2013, 705265 (2013).
   PubMedGoogle Scholar
• Cohn L, Delamarre L. Dendritic cell-targeted vaccines. Front. Immunol. 5, 255 (2014).
   PubMed Web of Science ®Google Scholar
• Lundstrom K. Self-replicating RNA viral vectors in vaccine development and gene therapy. Fut. Virol. 11, 345–356 (2016).
   Web of Science ®Google Scholar
• Shatkun AJ. Capping of eukaryotic mRNAs. Cell 9, 645–653 (1976).
   PubMed Web of Science ®Google Scholar
• McNamara MA, Nair SK, Holl EK. RNA-based vaccines in cancer immunotherapy. J. Immunol. Res. 2015, 794528 (2015).
   PubMed Web of Science ®Google Scholar
• Pasquinelli AE, Dahlberg JE, Lund E. Reverse 5′ caps in RNAs made in vitro by phage RNA polymerases. RNA 1, 957–967 (1995).
   PubMed Web of Science ®Google Scholar
• Stepinski J, Waddell C, Stolarski R, Darzynkiewicz E, Rhoads RE. Synthesis and properties of mRNAs containing the novel ‘anti-reverse’ cap analogs 7-methyl(3′-O-methyl)GpppG and 7-methyl(33′-deoxy)GpppG. RNA 7, 1486–1495 (2001).
   PubMed Web of Science ®Google Scholar
• Zohra FT, Chowdhury EH, Tada S, Hoshiba T, Akaike T. Effective delivery with enhanced translational activity synergistically accelerates mRNA-based transfection. Biochem. Biophys. Res. Comm. 358, 373–378 (2007).
   PubMed Web of Science ®Google Scholar
• Jaschke A, Hofer K, Nubel G, Frindert J. Cap-like structures in bacterial RNA and epitranscriptomic modification. Curr. Opin. Microbiol. 30, 44–49 (2016).
   PubMed Web of Science ®Google Scholar
• Cahova H, Winz ML, Hofer K, Nubel G, Jaschke A. NAD captureSeq indicates NAD as a bacterial cap for a subset of regulatory RNAs. Nature 519, 374–377 (2015).
   PubMed Web of Science ®Google Scholar
• Bird JG, Zhang Y, Tian Y et al. The mechanism of RNA 5′ capping with NAD+, NADH and dephospho-CoA. Nature 535, 444–447 (2016).
   PubMed Web of Science ®Google Scholar
• Bernstein P, Peltz SW, Ross J. The poly(A)-poly(A)-binding protein complex is a major determinant of mRNA stability in vitro. Mol. Cell. Biol. 9, 659–670 (1989).
   PubMed Web of Science ®Google Scholar
• Gingras A-C, Raught B, Sonenberg N. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Ann. Rev. Biochem. 68, 913–963 (1999).
   PubMed Web of Science ®Google Scholar
• Holtkamp S, Kreiter S, Selmi A et al. Modification of antigen-encoding RNA increases stability, translational efficacy, and T cell stimulatory capacity of dendritic cells. Blood 108, 4009–4017 (2006).
   PubMed Web of Science ®Google Scholar
• Munroe D, Jacobson A. mRNA Poly(A) tail a 3′ enhancer of translational initiation. Mol. Cell. Biol. 10, 3441–3455 (1990).
   PubMed Web of Science ®Google Scholar
• Mockey M, Gonçalves C, Dupuy FP, Lemoine FM, Pichon C, Midoux P. mRNA transfection of dendritic cells: synergistic effect of ARCA mRNA capping with Poly(A) chains in cis and in trans for a high protein expression level. Biochem. Biophys. Res. Comm. 340, 1062–1068 (2006).
   PubMed Web of Science ®Google Scholar
• Tcherepanova IY, Adams MD, Feng X et al. Ectopic expression of a truncated CD40L protein from synthetic posttranscriptionally capped RNA in dendritic cells induces high levels of IL-12 secretion. BMC Mol. Biol. 9, 90 (2008).
   PubMed Web of Science ®Google Scholar
• van der Velden AW, Thomas AA. The role of the 5′ untranslated region of an mRNA in translation regulation during development. Int. J. Biochem. Cell Biol. 31, 87–106 (1999).
   PubMed Web of Science ®Google Scholar
• Jansen RP. mRNA localization: message on the move. Nat. Rev. Mol. Cell Biol. 2, 247–256 (2001).
   PubMed Web of Science ®Google Scholar
• Bashirullah A, Cooperstock RL, Lipshitz HD. Spatial and temporal control of RNA stability. Proc. Natl Acad. Sci. USA 98, 7025–7028 (2001).
   PubMed Web of Science ®Google Scholar
• Turanov AA, Lobanov AV, Hatfield DL, Gladyshev VN. UGA-position dependent incorporation of selenocysteine into mammalian selenoproteins. Nucl. Acid Res. 41, 6952–6959 (2013).
   PubMed Web of Science ®Google Scholar
• Walczak R, Westhof E, Carbon P, Krol A. A novel RNA structural motif in the selenocysteine insertion element of eukaryotic selenoprotein mRNAs. RNA 2, 367–379 (1996).
   PubMed Web of Science ®Google Scholar
• Mignone F, Gissi C, Liuni S, Pesole G. Untranslated regions of mRNAs. Genome Biol. 3, 0004 (2002).
   Web of Science ®Google Scholar
• Deo RC, Bonanno JB, Sonenberg N, Burley SK. Recognition of polyadenylate RNA by the poly(A)-binding protein. Cell 98, 835–845 (1999).
   PubMed Web of Science ®Google Scholar
• Zhao Y, Moon E, Carpenito C et al. Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor. Cancer Res. 70, 9053–9061 (2010).
   PubMed Web of Science ®Google Scholar
• Kreiter S, Selmi A, Diken M et al. Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity. Cancer Res. 70, 9031–9040 (2010).
   PubMed Web of Science ®Google Scholar
• Kreiter S, Selmi A, Diken M et al. Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals. J. Immunology 180, 309–318 (2008).
   PubMed Web of Science ®Google Scholar
• Hornung V, Ellegast J, Kim S et al. 5′-Triphosphate RNA is the ligand for RIG-I. Science 314, 994–997 (2006).
   PubMed Web of Science ®Google Scholar
• Kariko K, Buckstein M, Ni H, Weissman D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005).
   PubMed Web of Science ®Google Scholar
• Kariko K, Muramatsu H, Welsh FA et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008).
   PubMed Web of Science ®Google Scholar
• Kariko K, Muramatsu H, Ludwig J, Weissman D. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucl. Acids Res. 39, e142 (2011).
   PubMed Web of Science ®Google Scholar
• Wolff JA, Malone RW, Williams P et al. Direct gene transfer into mouse muscle in vivo. Science 247, 4949, 1465–1468 (1990).
   PubMed Web of Science ®Google Scholar
• Conry RM, LoBuglio AF, Wright M et al. Characterization of a messenger RNA polynucleotide vaccine vector. Cancer Res. 55, 1397–1400 (1995).
   PubMed Web of Science ®Google Scholar
• Steitz J, Britten CM, Wolfel T, Tuting T. Effective induction of anti-melanoma immunity following genetic vaccination with synthetic mRNA coding for the fusion protein EGFP.TRP2. Cancer Immunol. Immunother. 55, 246–253 (2006).
   PubMed Web of Science ®Google Scholar
• Fotin-Mleczek M, Duchardt KM, Lorenz C et al. Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity. J. Immunother. 34, 1–15 (2011).
   PubMed Web of Science ®Google Scholar
• Houseley J, Tollervey D. The many pathways of RNA degradation. Cell 136, 763–776 (2009).
   PubMed Web of Science ®Google Scholar
• Probst J, Brechtel S, Scheel B et al. Characterization of the ribonuclease activity on the skin surface. Genetic Vacc. Ther. 4, 4 (2006).
   PubMedGoogle Scholar
• Qiu P, Ziegelhoffer P, Sun J, Yang NS. Gene gun delivery of mRNA in situ results in efficient transgene expression and genetic immunization. Gene Ther. 3, 262–268 (1996).
   PubMed Web of Science ®Google Scholar
• Dileo J, Miller TE Jr, Chesnoy S, Huang L. Gene transfer to subdermal tissues via a new gene gun design. Human Gene Ther. 14, 79–87 (2003).
   PubMed Web of Science ®Google Scholar
• Scheel B, Aulwurm S, Probst J et al. Therapeutic anti-tumor immunity triggered by injections of immunostimulating singlestrandedRNA. Eur. J. Immunol. 36, 2807–2816 (2006).
   PubMed Web of Science ®Google Scholar
• Scheel B, Teufel R, Probst J et al. Toll-like receptor-dependent activation of several human blood cell types by protamine condensed mRNA. Eur. J. Immunol. 35, 1557–1566 (2005).
   PubMed Web of Science ®Google Scholar
• Sköld AE, van Beek JJ, Sittig SP et al. Protamine-stabilized RNA as an ex vivo stimulant of primary human dendritic cell subsets. Cancer Immunol. Immunother. 64, 1461–1473 (2015).
   PubMed Web of Science ®Google Scholar
• Hoerr I, Obst R, Rammensee HG, Jung G. In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur. J. Immunol 30, 1–7 (2000).
   PubMed Web of Science ®Google Scholar
• Weide B, Pascolo S, Scheel B et al. Direct injection of protamine- protected mRNA: results of a Phase I/II vaccination trial in metastatic melanoma patients. J. Immunother. 32, 498–507 (2009).
   PubMed Web of Science ®Google Scholar
• McKee AS, Marrack P. Old and new adjuvants. Curr. Opin. Immunol. 47, 44–51 (2017).
   PubMed Web of Science ®Google Scholar
• Akasaki Y, Kikuchi T, Irie M et al. Cotransfection of Poly(I:C) and siRNA of IL-10 into fusions of dendritic and glioma cells enhances antitumor T helper type induction in patients with glioma. J. Immunother. 34, 121.128 (2011).
   PubMedGoogle Scholar
• Kreiter S, Diken M, Selmi A, Tureci O, Sahin U. Tumor vaccination using messenger RNA: prospects of a future therapy. Curr. Opin. Immunol. 23, 399–406 (2011).
   PubMed Web of Science ®Google Scholar
• Sahin U, Kariko K, Tureci O. mRNA-based therapeutics – developing a new class of drugs. Nature Rev. Drug Discov. 13, 759–780 (2014).
   PubMed Web of Science ®Google Scholar
• Schlake T, Thess A, Fotin-Mleczek M, Kallen K-J. Developing mRNA-vaccine technologies. RNA Biol. 9, 1319–1330 (2012).
   PubMed Web of Science ®Google Scholar
• Sayour EJ, Sanchez-Perez L, Flores C, Mitchell DA. Bridging infectious disease vaccines with cancer immunotherapy: a role for targeted RNA based immunotherapeutics. J. Immunother. Cancer 3, 13 (2015).
   PubMed Web of Science ®Google Scholar
• Bettinger T, Read ML. Recent developments in RNA based strategies for cancer gene therapy. Curr. Opin. Mol. Ther. 3, 116–124 (2001).
   PubMedGoogle Scholar
• Lu D, Benjamin R, Kim M, Conry RM, Curiel DT. Optimization of methods to achieve mRNA-mediated transfection of tumor cells in vitro and in vivo employing cationic liposome vectors. Cancer Gene Ther. 1, 245–252 (1994).
   PubMed Web of Science ®Google Scholar
• Wasungu L, Hoekstra D. Cationic lipids lipoplexes and intracellular delivery of genes. J. Control. Rel. 116, 255–264 (2006).
   PubMed Web of Science ®Google Scholar
• Little SR, Lynn DM, Ge Q et al. Poly-β amino estercontaining microparticles enhance the activity of nonviral genetic vaccines. Proc. Natl Acad. Sci. USA 101, 9534–9539 (2004).
   PubMed Web of Science ®Google Scholar
• Phua KKL, Leong KW, Nair SK. Transfection efficiency and transgene expression kinetics of mRNA delivered in naked and nanoparticle format. J. Control. Rel. 166, 227–233 (2013).
   PubMed Web of Science ®Google Scholar
• Su X, Fricke J, Kavanagh DG, Irvine DJ. In vitro and in vivo mRNA delivery using lipid-enveloped pH-responsive polymer nanoparticles. Mol. Pharmaceutics 8, 774–787 (2011).
   PubMed Web of Science ®Google Scholar
• Phua KKL, Nair SK, Leong KW. Messenger RNA (mRNA) nanoparticle tumour vaccination. Nanoscale 6, 7715–7729 (2014).
   PubMed Web of Science ®Google Scholar
• Phua KKL, Staats HF, Leong KW, Nair SK. Intranasal mRNA nanoparticle vaccination induces prophylactic and therapeutic anti-tumor immunity. Sci. Rep. 4, 5128 (2014).
   PubMed Web of Science ®Google Scholar
• Hess PR, Boczkowski D, Nair SK, Snyder D, Gilboa E. Vaccination with mRNAs encoding tumor-associated antigens and granulocyte-macrophage colony-stimulating factor efficiently primes CTL responses, but is insufficient to overcome tolerance to a model tumor/self antigen. Cancer Immunol. Immunother. 55, 672–683 (2006).
   PubMed Web of Science ®Google Scholar
• Mockey M, Bourseau E, Chandrashekhar V et al. mRNA-based cancer vaccine: prevention of B16 melanoma progression and metastasis by systemic injection of MART1 mRNA histidylated lipoplexes. Cancer Gene Ther. 14, 802–814 (2007).
   PubMed Web of Science ®Google Scholar
• Perche F, Benvegnu T, Berchel M et al. Enhancement of dendritic cells transfection in vivo and of vaccination against B16F10 melanoma with mannosylated histidylated lipopolyplexes loaded with tumor antigen messenger RNA. Nanomedicine 7, 445–453 (2011).
   PubMed Web of Science ®Google Scholar
• Boczkowski D, Nair SK, Snyder D, Gilboa E. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J. Exp. Med. 184, 465–472 (1996).
   PubMed Web of Science ®Google Scholar
• Nair SK, Hull S, Coleman D, Gilboa E, Lyerly HK, Morse MA. Induction of carcinoembryonic antigen (CEA)-specific cytotoxic T-lymphocyte responses in vitro using autologous dendritic cells loaded with CEA peptide or CEA RNA in patients with metastatic malignancies expressing CEA. Int. J. Cancer 82, 121–124 (1999).
   PubMed Web of Science ®Google Scholar
• Ponsaerts P, Van Tendeloo VFI, Berneman ZN. Cancer immunotherapy usingRNA-loaded dendritic cells. Clin. Exp. Immunol. 134, 378–384 (2003).
   PubMed Web of Science ®Google Scholar
• Schuler G, Schuler-Thurner B, Steinman RM. The use of dendritic cells in cancer immunotherapy. Cur. Opin. Immunol. 15, 138–147 (2003).
   PubMed Web of Science ®Google Scholar
• Heiser A, Coleman D, Dannull J et al. Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors. J. Clin. Invest. 109, 409–417 (2002).
   PubMed Web of Science ®Google Scholar
• Morse MA, Nair SK, Boczkowski D et al. The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer. Intl. J. Gastrointest. Cancer 32, 1–6 (2002).
   PubMedGoogle Scholar
• Morse MA, Nair SK, Mosca PJ et al. Immunotherapy with autologous, human dendritic cells transfected with carcinoembryonic antigen mRNA. Cancer Invest. 21, 341–349 (2003).
   PubMed Web of Science ®Google Scholar
• Caruso DA, Orme LM, Neale AM et al. Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer. Neuro-Oncology 6, 236–246 (2004).
   PubMed Web of Science ®Google Scholar
• Nair SK, Morse M, Boczkowski D et al. Induction of tumor specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells. Ann. Surg. 235, 540–549 (2002).
   PubMed Web of Science ®Google Scholar
• Su Z, Dannull J, Heiser A et al. Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res. 63, 2127–2133 (2003).
   PubMed Web of Science ®Google Scholar
• Dannull J, Su Z, Rizzieri D et al. Enhancement of vaccine mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest. 115, 3623–3633 (2005).
   PubMed Web of Science ®Google Scholar
• Bonehill A, Van Nuffel AMT, Corthals J et al. Single step antigen loading and activation of dendritic cells by mRNA electroporation for the purpose of therapeutic vaccination in melanoma patients. Clin. Cancer Res. 15, 3366–3375 (2009).
   PubMed Web of Science ®Google Scholar
• Kyte JA, Kvalheim G, Aamdal S, Sæb⊘e-Larssen S, Gaudernack G. Preclinical full-scale evaluation of dendritic cells transfected with autologous tumor-mRNA for melanoma vaccination. Cancer Gene Ther. 12, 579–591 (2005).
   PubMed Web of Science ®Google Scholar
• Schuurhuis DH, Verdijk P, Schreibelt G et al. In situ expression of tumor antigens by messenger RNA-electroporated dendritic cells in lymph nodes of melanoma patients. Cancer Res. 69, 2927–2934 (2009).
   PubMed Web of Science ®Google Scholar
• Strauss JH, Strauss EG. The alphaviruses: gene expression, replication, and evolution. Microbiol. Rev. 58, 491–562 (1994).
   PubMedGoogle Scholar
• Pijlman GP, Suhrbier A, Khromykh AA. Kunjin virus replicons: an RNA-based, non-cytopathic viral vector system for protein production, vaccine and gene therapy applications. Exp. Opin. Biol. Ther. 6, 134–145 (2006).
   Web of Science ®Google Scholar
• Osakada F, Callaway EM. Design and generation of recombinant rabies virus vectors. Nat. Protoc. 8(8), 1583–1601 (2013).
   PubMed Web of Science ®Google Scholar
• An H, Kim GN, Kang CY. Genetically modified VSV(NJ) vector is capable of accommodating a large foreign gene insert and allows high level gene expression. Virus Res. 171(1), 168–177 (2013).
   PubMed Web of Science ®Google Scholar
• Radecke F, Spielhofer P, Schneider H et al. Rescue of measles viruses from cloned DNA. EMBO J. 14(23), 5773–5784 (1995).
   PubMed Web of Science ®Google Scholar
• Pyankov OV, Bodnev SA, Pyankova OG et al. A Kunjin replicon virus-like vaccine provides protection against Ebola virus infection in nonhuman primates. J. Infect. Dis. 212(Suppl. 2), S368–S371 (2015).
   PubMedGoogle Scholar
• Marzi A, Robertson SJ, Haddock E et al. Ebola vaccine. VSV-EBOV rapidly protects macaques against infection with the 2014/2015 Ebola virus outbreak strain. Science 349, 739–742 (2015).
   PubMed Web of Science ®Google Scholar
• Wilson JA, Hart MK. Protection from Ebola virus mediated by cytotoxic T-lymphocytes specific for the viral nucleoprotein. J. Virol. 75, 2660–2664 (2001).
   PubMed Web of Science ®Google Scholar
• Huttner A, Dayer JA, Yerly S et al. The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomized double-blind, placebo-controlled Phase I/II trial. Lancet Infect. Dis. 15, 1156–1166 (2015).
   PubMed Web of Science ®Google Scholar
• Hu HM, Chen HW, Hsiao Y et al. The successful induction of T-cell and antibody responses by a recombinant measles virus-vectored tetravalent dengue vaccine provides partial protection against dengue-2 infection. Hum. Vaccin. Immunother. 12, 1678–1689 (2016).
   PubMed Web of Science ®Google Scholar
• Kamrud KI, Coffield VM, Owens G et al. In vitro and in vivo characterization of microRNA-targeted alphavirus replicon and helper RNAs. J. Virol. 84, 7713–7725 (2010).
   PubMed Web of Science ®Google Scholar
• Bhomia M, Sharma A, Gayen M et al. Artificial microRNAs can effectively inhibit replication of Venezuelan equine encephalitis virus. Antivir. Res. 100, 429–434 (2013).
   PubMed Web of Science ®Google Scholar
• Hoang-Le D, Smeenk L, Anraku I et al. A Kunjin replicon vector encoding granulocyte macrophage colony-stimulating factor for intra-tumoral gene therapy. Gene Ther. 16(2), 190–199 (2009).
   PubMed Web of Science ®Google Scholar
• Garcia-Hernandez ML, Gray A, Hubby B, Klinger OJ, Kast WM. Prostate stem cell antigen vaccination induces a long-term protective immune response against prostate cancer in the absence of autoimmunity. Cancer Res. 68, 861–869 (2008).
   PubMed Web of Science ®Google Scholar
• Martikainen M, Niittykoski M, von und zu Frauenberg M et al. MicroRNA-attenuated clone of virulent Semliki Forest virus overcomes antiviral type I interferon in resistant mouse CT-2A glioma. J. Virol. 89, 10637–10647 (2015).
   PubMed Web of Science ®Google Scholar
• Ying H, Zaks TZ, Wang RF et al. Cancer therapy using a self-replicating RNA vaccine. Nat. Med. 5, 823–827 (1999).
   PubMed Web of Science ®Google Scholar
• Pepini T, Pulichino AM, Carsillo T et al. Induction of an IFN-mediated antiviral response by a self-amplifying RNA vaccine: implications for vaccine design. J. Immunol. 198, 4012–4024 (2017).
   PubMed Web of Science ®Google Scholar
• Démoulins T, Englezou PC, Milona P et al. Self-replicating RNA vaccine delivery to dendritic cells. Methods Mol. Biol. 1499, 37–75 (2017).
   PubMedGoogle Scholar
• Beissert T, Koste L, Perkovic M et al. Improvement of in vivo expression of genes delivered by self-amplifying RNA using vaccinia virus immune evasion proteins. Hum. Gene Ther. 28, 1138–1146 (2017).
   PubMed Web of Science ®Google Scholar
• Slovin SF, Kehoe M, Durso R et al. A Phase I dose escalation trial of vaccine replicon particles (VRP) expressing prostate-specific membrane antigen (PSMA) in subjects with prostate cancer. Vaccine 31, 943–949 (2013).
   PubMed Web of Science ®Google Scholar
• Lundstrom K, Boulikas T. Breakthrough in cancer therapy: encapsulation of drugs and viruses. Curr Drug Discov. 11, 19–23 (2002).
   Google Scholar
• Lundstrom K. RNA-based drugs and vaccines. Exp. Rev. Vacc. 14, 253–263 (2015).
   PubMed Web of Science ®Google Scholar
• Schultheis B, Strumberg D, Santel A et al. First-in-human phase I study of the liposomal RNA interference therapeutic Atu027 in patients with advanced solid tumors. J. Clin. Oncol. 32, 4141–4148 (2014).
   PubMed Web of Science ®Google Scholar
• Arbutus Biopharma. ARB-1467 ( RNAi). www.arbutusbio.com/portfolio/arb-1467-rnai.php.
   Google Scholar
• Quark QPI-1007. http://quarkpharma.com/?page_id=23.
   Google Scholar
• Moderna Therapeutics. Pipeline. www.modernatx.com/pipeline.
   Google Scholar
• Tian H, Zhou C, Yang J, Li J, Gong Z. Long and short noncoding RNAs in lung cancer precision medicine: Opportunities and challenges. Tumour Biol. 39(4), 1010428317697578 (2017).
   Google Scholar
• Pardi N, Hogan MJ, Pelc RS et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature 543, 248–251 (2017).
   PubMed Web of Science ®Google Scholar
• Reynard O, Mokhonov V, Mokhonova E et al. Kunjin virus replicon-based vaccines expressing Ebola virus glycoprotein GP protect the guinea pig against lethal Ebola virus infection. J. Infect. Dis. 204(Suppl. 3), S1060–S1065 (2011).
   PubMedGoogle Scholar
• Pushko P, Bray M, Ludwig GV et al. Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus. Vaccine 19, 142–153 (2000).
   PubMed Web of Science ®Google Scholar
• Anraku I, Mokhonov VV, Rattanasena P et al. Kunjin replicon-based simian immunodeficiency virus gag vaccines. Vaccine 26, 3268–3276 (2008).
   PubMed Web of Science ®Google Scholar
• Grabbe S, Haas H, Diken M, Kranz LM, Langguth P, Sahin U. Translating nanoparticulate-personalized cancer vaccines into clinical applications: case study with RNA-lipoplexes for the treatment of melanoma. Nanomedicine 11, 2723–2734 (2016).
   PubMed Web of Science ®Google Scholar
• Heesen L, Jabulowksy R, Loquai C et al. A first-in-human Phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles encoding shared tumor antigens for potent immunotherapy. Presented at: ESMO Oncology-Immunology Congress 2017. Geneva, Switzerland, 7–10 December 2017 ( Poster 49P).
   Google Scholar
• Gousseinov E, Kozlov M, Scanlan C et al. RNA-based therapeutics and vaccines. Genetic Engineering & Biotechnology News. 15 September 2015. www.genengnews.com/gen-exclusives/rna-based-therapeutics-and-vaccines/77900520.
   Google Scholar