THE CURRENT STRATEGIES, RECENT PROGRESS AND REMAINING CHALLENGES FOR DEVELOPING MRNA VIRAL VACCINE

Main Article Content

Priscilla Felicia Apriliani Irawan
Budiman Bela

Abstract

The mRNA expression system has revolutionised biotechnology, notably in viral mRNA vaccine development, cancer immunotherapy, and gene therapy. However, recent safety concerns regarding the COVID-19 mRNA vaccine have emerged, particularly regarding its rare adverse effects and its possible connection to cancer. This review explains several approaches used in developing viral mRNA vaccines, the past obstacles solved in generating the current COVID-19 mRNA vaccine, and finally the current advancements and ongoing challenges in the viral mRNA vaccine field. We particularly focus on strategies and methods to improve the safety and translation efficiency of the mRNA vaccine, such as enhancing the vaccine’s transfection specificity to targeted dendritic cells (DC) and using viral IRES or self-amplifying mRNA format to improve mRNA translation efficiency.

Article Details

How to Cite
Irawan, P. F. A., & Bela, B. (2024). THE CURRENT STRATEGIES, RECENT PROGRESS AND REMAINING CHALLENGES FOR DEVELOPING MRNA VIRAL VACCINE. Jurnal Bioteknologi Dan Biosains Indonesia, 11(1), 121–137. Retrieved from https://ejournal.brin.go.id/JBBI/article/view/6422
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References

Akiyama BM, Eiler D, Kieft JS (2016) Struc-tured RNAs that evade or confound exonucleases: function follows form. Curr Opin Struct Biol 36:40–47. https://doi.org/10.1016/j.sbi.2015.12.006

Ammirati E, Cooper LT (2022) Recovery from mRNA COVID-19 vaccine-related myocarditis. Lancet Child

Adolesc Health 6:749–751. https://doi.org/10.1016/S2352-4642(22)00272-3

Anderson BR, Muramatsu H, Jha BK, Sil-verman RH, Weissman D, Kariko K (2011) Nucleoside modifications in RNA limit activation of 2’-5’-oligoadenylate synthetase and in-crease resistance to cleavage by RNase L.

Nucleic Acids Res 39:9329–9338. https://doi.org/10.1093/nar/gkr586

Anderson BR, Muramatsu H, Nallagatla SR, Bevilacqua PC, Sansing LH,

Weissman D, Karikó K (2010) Incor-poration of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res 38:5884–5892. https://doi.org/10.1093/nar/gkq347

Andries O, Mc Cafferty S, De Smedt SC, Weiss R, Sanders NN, Kitada T (2015) N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expres-sion and reduced immunogenicity in mammalian cell lines and mice. Jour-nal of Controlled Release 217:337–344. https://doi.org/10.1016/j.jconrel.2015.08.051

Beverly M, Dell A, Parmar P, Houghton L (2016) Label-free analysis of mRNA capping efficiency using RNase H probes and LC-MS. Anal Bioanal Chem 408:5021–5030. https://doi.org/10.1007/s00216-016-9605-x

Biziaev N, Shuvalov A, Salman A, Egorova T, Shuvalova E, Alkalaeva E (2024) The impact of mRNA poly(A) tail length on eukaryotic translation stag-es. Nucleic Acids Res 52:7792–7808. https://doi.org/10.1093/nar/gkae510

Bloom K, van den Berg F, Arbuthnot P (2021) Self-amplifying RNA vaccines for infectious diseases. Gene Ther 28:117–129. https://doi.org/10.1038/s41434-020-00204-y

Clemente B, Denis M, Silveira CP, Schia-vetti F, Brazzoli M, Stranges D (2023) Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design. Front Immunol 14. https://doi.org/10.3389/fimmu.2023.1294929

Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, Himansu S, Schäfer A, Ziwawo CT, DiPiazza AT, Dinnon KH, Elbashir SM, Shaw CA, Woods A, Fritch EJ,

Martinez DR, Bock KW, Minai M, Na-gata BM, Hutchinson GB, Wu K, Hen-ry C, Bahl K, Garcia-Dominguez D, Ma LZ, Renzi I, Kong WP, Schmidt SD, Wang L, Zhang Y, Phung E, Chang LA, Loomis RJ, Altaras NE, Narayanan E, Metkar M, Presnyak V, Liu C, Louder MK, Shi W, Leung K, Yang ES, West A, Gully KL, Stevens LJ, Wang N, Wrapp D, Doria-Rose NA, Stewart-Jones G, Bennett H, Al-varado GS, Nason MC, Ruckwardt TJ, McLellan JS, Denison MR, Chap-pell JD, Moore IN, Morabito KM, Mas-cola JR, Baric RS, Carfi A, Graham BS (2020) SARS-CoV-2 mRNA vac-cine design enabled by prototype pathogen preparedness. Nature 586:567–571. https://doi.org/10.1038/s41586-020-2622-0

Costanzo M, De Giglio MAR, Roviello GN (2023) Deciphering the Relationship between SARS-CoV-2 and Cancer. Int J Mol Sci 24:7803. https://doi.org/10.3390/ijms24097803

Deviatkin AA, Simonov RA, Trutneva KA, Maznina AA, Soroka AB, Kogan AA, Feoktistova SG, Khavina EM, Mityae-va ON, Volchkov PY (2023) Cap-Independent Circular mRNA Transla-tion Efficiency. Vaccines (Basel) 11:238. https://doi.org/10.3390/vaccines11020238

Doğru Y, Kehaya S (2022) Do Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines Change Creutzfeldt-Jakob Disease Prognosis? Balkan Med J 39:381–382. https://doi.org/10.4274/balkanmedj.galenos.2022.2022-6-83

Drazkowska K, Tomecki R, Warminski M, Baran N, Cysewski D, Depaix A, Kasprzyk R, Kowalska J, Jemielity J, Sikorski PJ (2022) 2′- O -Methylation of the second transcribed nucleotide within the mRNA 5′ cap impacts the protein production level in a cell-specific manner and contributes to RNA immune evasion. Nucleic Acids Res 50:9051–9071. https://doi.org/10.1093/nar/gkac722

Elizalde MU, Eguinoa FJG, de las Huertas AGL, Jiménez-González M, Ramírez E (2024) Myocarditis and pericarditis risk with mRNA COVID-19 vaccina-tion compared to unvaccinated indi-viduals: A retrospective cohort study in a Spanish Tertiary Hospital. Bio-medicine & Pharmacotherapy 171:116181. https://doi.org/10.1016/j.biopha.2024.116181

Fang E, Liu X, Li M, Zhang Z, Song L, Zhu B, Wu X, Liu J, Zhao D, Li Y (2022) Advances in COVID-19 mRNA vac-cine development. Signal Transduct Target Ther 7:94. https://doi.org/10.1038/s41392-022-00950-y

Galloway A, Cowling VH (2019) mRNA cap regulation in mammalian cell function and fate. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mech-anisms 1862:270–279. https://doi.org/10.1016/j.bbagrm.2018.09.011

Gibo M, Kojima S, Fujisawa A, Kikuchi T, Fukushima M (2024) Increased Age-Adjusted Cancer Mortality After the Third mRNA-Lipid Nanoparticle Vac-cine Dose During the COVID-19 Pan-demic in Japan. Cureus. https://doi.org/10.7759/cureus.57860

Gómez-Carballa A, Martinón-Torres F, Salas A (2022) Is SARS-CoV-2 an oncogenic virus? Journal of Infection 85:573–607. https://doi.org/10.1016/j.jinf.2022.08.005

Hein S, Herrlein M, Mhedhbi I, Bender D, Haberger V, Benz N, Eisert J, Stingl J, Dreher M, Oberle D, Schulze J, Mache C, Budt M, Hildt C, Wolff T, Hildt E (2022) Analysis of BNT162b2‐ and CVnCoV‐elicited sera and of con-valescent sera toward SARS‐CoV‐2 viruses. Allergy 77:2080–2089. https://doi.org/10.1111/all.15189

Hibino M, Uryu K, Takeda T, Kunimatsu Y, Shiotsu S, Uchino J, Hirai S, Yamada T, Okada A, Hasegawa Y, Hiranuma O, Chihara Y, Kamada R, Tobe S, Maeda K, Horiuchi S, Kondo T,

Takayama K (2022) Safety and Im-munogenicity of mRNA Vaccines Against Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Lung Cancer Receiving Immune

Checkpoint Inhibitors: A Multicenter Observational Study in Japan. Journal of Thoracic Oncology 17:1002–1013. https://doi.org/10.1016/j.jtho.2022.05.015

Husby A, Køber L (2022) COVID-19 mRNA vaccination and myocarditis or peri-carditis. The Lancet 399:2168–2169. https://doi.org/10.1016/S0140-6736(22)00842-X

Hyde JL, Diamond MS (2015) Innate im-mune restriction and antagonism of vi-ral RNA lacking 2׳-O methylation. Vi-rology 479–480:66–74. https://doi.org/10.1016/j.virol.2015.01.019

Jalkanen AL, Coleman SJ, Wilusz J (2014) Determinants and implications of mRNA poly(A) tail size – Does this protein make my tail look big? Semin Cell Dev Biol 34:24–32. https://doi.org/10.1016/j.semcdb.2014.05.018

Karikó K, Buckstein M, Ni H, Weissman D (2005) Suppression of RNA recogni-tion by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23:165–175. https://doi.org/10.1016/j.immuni.2005.06.008

Karikó K, Muramatsu H, Ludwig J, Weiss-man D (2011) Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and im-proves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res 39. https://doi.org/10.1093/nar/gkr695

Karikó K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S, Weissman D (2008) Incorporation of pseudouridine into mRNA yields superior nonimmu-nogenic vector with increased transla-tional capacity and biological stability. Molecular Therapy 16:1833–1840. https://doi.org/10.1038/mt.2008.200

Karikó K, Ni H, Capodici J, Lamphier M, Weissman D (2004) mRNA Is an

Endogenous Ligand for Toll-like Re-ceptor 3. Journal of Biological Chem-istry 279:12542–12550. https://doi.org/10.1074/jbc.M310175200

Ko HL, Park HJ, Kim J, Kim H, Youn H, Nam JH (2019) Development of an RNA expression platform controlled by viral

internal ribosome entry sites. J Micro-biol Biotechnol 29:127–140. https://doi.org/10.4014/jmb.1811.11019

Kranz LM, Diken M, Haas H, Kreiter S, Lo-quai C, Reuter KC, Meng M, Fritz D, Vascotto F, Hefesha H, Grunwitz C, Vormehr M, Hüsemann Y, Selmi A, Kuhn AN, Buck J, Derhovanessian E, Rae R, Attig S, Diekmann J, Jabulow-sky RA, Heesch S, Hassel J, Langguth P, Grabbe S, Huber C, Tü-reci Ö, Sahin U (2016) Systemic RNA delivery to dendritic cells exploits anti-viral defence for cancer immunothera-py. Nature 534:396–401. https://doi.org/10.1038/nature18300

Kremsner PG, Ahuad Guerrero RA, Arana-Arri E, Aroca Martinez GJ, Bonten M, Chandler R, Corral G, De Block EJL, Ecker L, Gabor JJ, Garcia Lopez CA, Gonzales L, Granados González MA, Gorini N, Grobusch MP, Hrabar AD, Junker H, Kimura A, Lanata CF, Leh-mann C, Leroux-Roels I, Mann P, Martinez-Reséndez MF, Ochoa TJ, Poy CA, Reyes Fentanes MJ, Rivera Mejia LM, Ruiz Herrera VV, Sáez-Llorens X, Schönborn-Kellenberger O, Schunk M, Sierra Garcia A, Vergara I, Verstraeten T, Vico M, Oostvogels L, Lovesio L, Diez F, Grazziani F, Ga-naha MC, Zalatnik VJ, Dittrich RJ, Espínola L, Lambert S, Longhi A, Vecchio C, Mastruzzo M, Fernandez A, Borchowiek S, Potito R, Ahuad Guerrero RA, Guardiani FM, Castella S, Foccoli M, Pedernera A, Braida A, Durigan V, Martella C, Bobat A, Bog-gia BE, Nemi SA, Tartaglione JG, Piedimonte FC, De Bie J, Reynales Londoño H, Rodríguez Ordoñez PA, García Cruz JM, Bautista Toloza L, Ladino González MC, Zambrano Ochoa AP, Prieto Pradera I, Torres Hernandez D, Mazo Elorza DP,

Collazos Lennis MF, Vanegas Dominguez B, Solano Mosquera LM, Fendel R, Fleischmann WA, Koehne E, Kreidenweiss A, Köhler C, Esen M, Horn C, Eberts S, Kroidl A, Huber K, Thiel V, Mazara Rosario S, Reyes G, Rivera L, Donastorg Y, Lantigua F, Torres Almanzar D, Candelario R, Peña Mendez L, Rosario Gomez N, Portolés-Pérez A, Ascaso del Río A, Laredo Velasco L, Bustinduy Odriozo-la MJ, Larrea Arranz I, Martínez Al-corta LI, Durán Laviña MI, Imaz-Ayo N, Meijide S, García-de-Vicuña A, Santorcuato A, Gallego M, Aguirre-García GM, Olmos Vega J, González Limón P, Vázquez Villar A, Chávez Barón J, Arredondo Saldaña F, Luján Palacios J de D, Camacho Choza LJ, Vázquez Saldaña EG, Ortega Dominguez SJ, Vega Orozco KS, Torres Quiroz IA, Martinez Avendaño A, Herrera Sanchez J, Guzman E, Castro Castrezana L, Ruiz Palacios y Santos GM, de Winter RFJ, de Jonge HK, Schnyder JL, Boersma W, Hes-sels L, Djamin R, van der Sar S, DeAntonio R, Peña M, Rebollon G, Rojas M, Escobar J, Hammerschlag Icaza B, Wong T DY, Barrera Peri-gault P, Ruiz S, Chan M, Arias Hoo DJ, Gil AI, Celis CR, Balmaceda MP, Flores O, Ochoa M, Peña B, de la Flor C, Webb CM, Cornejo E, Sanes F, Mayorga V, Valdiviezo G, Ramírez Lamas SP, Grandez Castillo GA, La-ma JR, Matta Aguirre ME, Arancibia Luna LA, Carbajal Paulet Ó, Zambra-no Ortiz J, Camara A, Guzman Quin-tanilla F, Diaz-Parra C, Morales-Oliva J, Cornejo RE, Ricalde SA, Vidal J, Rios Nogales L, Cheatham-Seitz D, Gregoraci G, Brecx A, Walz L, Vahr-enhorst D, Seibel T, Quintini G (2022) Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candi-date in ten countries in Europe and Latin America (HERALD): a random-ised, observer-blinded, placebo-controlled, phase 2b/3 trial. Lancet In-fect Dis 22:329–340. https://doi.org/10.1016/S1473-3099(21)00677-0

Kühn U, Gündel M, Knoth A, Kerwitz Y, Rüdel S, Wahle E (2009) Poly(A) tail length is controlled by the nuclear Poly(A)-binding protein regulating the interaction between Poly(A) polymer-ase and the cleavage and

polyadenylation specificity factor. Journal of Biological Chemistry 284:22803–22814. https://doi.org/10.1074/jbc.M109.018226

Kühn U, Wahle E (2004) Structure and func-tion of poly(A) binding proteins. Bio-chimica et Biophysica Acta - Gene Structure and Expression 1678:67–84. https://doi.org/10.1016/j.bbaexp.2004.03.008

Kuvandık A, Özcan E, Karaduman S, Sun-gurtekin H (2022) Creutzfeldt-Jakob Disease After the Coronavirus Dis-ease-2019 Vaccination. Turkish Jour-nal of Intensive Care 20:61–64. https://doi.org/10.4274/tybd.galenos.2021.91885

Leppek K, Das R, Barna M (2018) Func-tional 5′ UTR mRNA structures in eu-karyotic translation regulation and how to find them. Nat Rev Mol Cell Biol 19:158–174. https://doi.org/10.1038/nrm.2017.103

Liu A, Wang X (2022) The Pivotal Role of Chemical Modifications in mRNA Therapeutics. Front Cell Dev Biol 10. https://doi.org/10.3389/fcell.2022.901510

Liu C, Zhang L, Liu H, Cheng K (2017) De-livery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications. Journal of Controlled Re-lease 266:17–26. https://doi.org/10.1016/j.jconrel.2017.09.012

Lloyd RE (2015) Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses. Virology 479–480:457–474. https://doi.org/10.1016/j.virol.2015.03.001

Lozano G, Martínez-Salas E (2015) Struc-tural insights into viral IRES-dependent translation mechanisms. Curr Opin Virol 12:113–120. https://doi.org/10.1016/j.coviro.2015.04.008

Mailliot J, Martin F (2018) Viral internal ribo-somal entry sites: four classes for one goal. Wiley Interdiscip Rev RNA 9. https://doi.org/10.1002/wrna.1458

Martinez-Salas E, Francisco-Velilla R, Fer-nandez-Chamorro J, Embarek AM (2018) Insights into structural and mechanistic features of viral IRES

elements. Front Microbiol 8. https://doi.org/10.3389/fmicb.2017.02629

Matsumiya T, Shiba Y, Ding J, Kawaguchi S, Seya K, Imaizumi T (2023) The double‐stranded RNA‐dependent pro-tein kinase PKR negatively regulates the protein expression of IFN‐β in-duced by RIG-I signaling. The FASEB Journal 37. https://doi.org/10.1096/fj.202201520RR

Mayr C (2019) What Are 3′ UTRs Doing? Cold Spring Harb Perspect Biol 11:a034728. https://doi.org/10.1101/cshperspect.a034728

Mayr C (2017) Regulation by 3′-Untranslated Regions. Annu Rev Genet 51:171–194. https://doi.org/10.1146/annurev-genet-120116-024704

McCormick K, Moreno Herrero J, Haas H, Fattah S, Heise A, O’Brien FJ, Cryan S-A (2024) Optimizing the Delivery of mRNA to Mesenchymal Stem Cells for Tissue Engineering Applications. Mol Pharm 21:1662–1676. https://doi.org/10.1021/acs.molpharmaceut.3c00898

McGee JE, Kirsch JR, Kenney D, Cerbo F, Chavez EC, Shih T-Y, Douam F, Wong WW, Grinstaff MW (2024) Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency. Nat Biotech-nol. https://doi.org/10.1038/s41587-024-02306-z

McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A (2015) Type I interferons in infectious disease. Nat Rev Immunol 15:87–103. https://doi.org/10.1038/nri3787

Miao L, Zhang Y, Huang L (2021) mRNA vaccine for cancer immunotherapy. Mol Cancer 20:41. https://doi.org/10.1186/s12943-021-01335-5

Pateev I, Seregina K, Ivanov R, Resh-etnikov V (2023) Biodistribution of RNA Vaccines and of Their Products: Evidence from Human and Animal Studies. Biomedicines 12:59. https://doi.org/10.3390/biomedicines12010059

Picard-Jean F, Brand C, Tremblay-Létourneau M, Allaire A, Beaudoin MC, Boudreault S, Duval C, Rainville-Sirois J, Robert F, Pelletier J, Geiss BJ, Bisaillon M (2018) 2’-O-methylation of the mRNA cap protects RNAs from decapping and degrada-tion by DXO. PLoS One 13:e0193804. https://doi.org/10.1371/journal.pone.0193804

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roy-choudhury S, Koury K, Li P, Kalina W V., Cooper D, Frenck RW, Hammitt LL, Türeci Ö, Nell H, Schaefer A, Ünal S, Tresnan DB, Mather S, Dormitzer PR, Şahin U, Jansen KU, Gruber WC (2020) Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine 383:2603–2615. https://doi.org/10.1056/NEJMoa2034577

Popovitz J, Sharma R, Hoshyar R, Soo Kim B, Murthy N, Lee K (2023) Gene edit-ing therapeutics based on mRNA de-livery. Adv Drug Deliv Rev 200:115026. https://doi.org/10.1016/j.addr.2023.115026

Ramanathan A, Robb GB, Chan S-H (2016) mRNA capping: biological functions and applications. Nucleic Acids Res 44:7511–7526. https://doi.org/10.1093/nar/gkw551

Rosa SS, Prazeres DMF, Azevedo AM, Marques MPC (2021) mRNA vaccines manufacturing: Challenges and bot-tlenecks. Vaccine 39:2190–2200. https://doi.org/10.1016/j.vaccine.2021.03.038

Sasaki K, Sato Y, Okuda K, Iwakawa K, Harashima H (2022) mRNA-Loaded Lipid Nanoparticles Targeting Dendrit-ic Cells for Cancer Immunotherapy. Pharmaceutics 14:1572. https://doi.org/10.3390/pharmaceutics14081572

Schult P, Roth H, Adams RL, Mas C, Imbert L, Orlik C, Ruggieri A, Pyle AM, Lohmann V (2018) microRNA-122 amplifies hepatitis C virus translation by shaping the structure of the internal ribosomal entry site. Nat Commun 9:2613. https://doi.org/10.1038/s41467-018-05053-3

Schwartz SL, Conn GL (2019) RNA regula-tion of the antiviral protein 2′‐5′‐oligoadenylate synthetase. WIREs RNA 10. https://doi.org/10.1002/wrna.1534

Solis O, Beccari AR, Iaconis D, Talarico C, Ruiz-Bedoya CA, Nwachukwu JC, Cimini A, Castelli V, Bertini R, Mon-topoli M, Cocetta V, Borocci S, Prandi IG, Flavahan K, Bahr M, Napiorkowski A, Chillemi G, Ooka M, Yang X, Zhang S, Xia M, Zheng W, Bonaven-tura J, Pomper MG, Hooper JE, Mo-rales M, Rosenberg AZ, Nettles KW, Jain SK, Allegretti M, Michaelides M (2022) The SARS-CoV-2 spike pro-tein binds and modulates estrogen re-ceptors. Sci Adv 8. https://doi.org/10.1126/sciadv.add4150

Spiliopoulou P, Janse van Rensburg HJ, Avery L, Kulasingam V, Razak A, Be-dard P, Hansen A, Chruscinski A, Wang B, Kulikova M, Chen R, Speers V, Nguyen A, Lee J, Coburn B, Spreafico A, Siu LL (2023) Longitudi-nal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy. Cell Death Dis 14:49. https://doi.org/10.1038/s41419-022-05548-4

Tan X, Wan Y (2008) Enhanced protein ex-pression by internal ribosomal entry site-driven mRNA translation as a novel approach for in vitro loading of dendritic cells with antigens. Hum Immunol 69:32–40. https://doi.org/10.1016/j.humimm.2007.11.009

Tatematsu M, Funami K, Seya T, Matsumo-to M (2018). Extracellular RNA Sens-ing by Pattern Recognition

Receptors. J Innate Immun 10:398–406. https://doi.org/10.1159/000494034

Tetz G, Tetz V (2022) Prion-like Domains in Spike Protein of SARS-CoV-2 Differ across Its Variants and Enable Changes in Affinity to ACE2. Microor-ganisms 10:280. https://doi.org/10.3390/microorganisms10020280

Vlatkovic I, Ludwig J, Boros G, Szabó GT, Reichert J, Buff M, Baiersdörfer M, Reinholz J, Mahiny AJ, Şahin U, Kari-kó K (2022) Ribozyme Assays to Quantify the Capping Efficiency of In Vitro-Transcribed mRNA. Pharmaceu-tics 14:328. https://doi.org/10.3390/pharmaceutics14020328

Wong H-L, Hu M, Zhou CK, Lloyd PC, Amend KL, Beachler DC, Secora A, McMahill-Walraven CN, Lu Y, Wu Y, Ogilvie RP, Reich C, Djibo DA, Wan Z, Seeger JD, Akhtar S, Jiao Y, Chil-larige Y, Do R, Hornberger J, Obidi J, Forshee R, Shoaibi A, Anderson SA (2022) Risk of myocarditis and peri-carditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases. The Lancet 399:2191–2199. https://doi.org/10.1016/S0140-6736(22)00791-7

Xia X (2021) Detailed Dissection and Criti-cal Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines. Vac-cines (Basel) 9:734. https://doi.org/10.3390/vaccines9070734

Zhang S, El-Deiry WS (2024) Transfected SARS-CoV-2 spike DNA for mamma-lian cell expression inhibits p53 acti-vation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2 proteins in cancer cells and increases cancer cell viability after chemotherapy exposure. Oncotarget 15:275–284. https://doi.org/10.18632/oncotarget.28582

Zhou W, Jiang L, Liao S, Wu F, Yang G, Hou L, Liu L, Pan X, Jia W, Zhang Y (2023) Vaccines’ New Era-RNA Vac-cine. Viruses 15:1760. https://doi.org/10.3390/v15081760

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