For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
53
views
301
references
 Top references
cited by
126
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
2 collections
    0
    shares
      507
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Self-assembled mRNA vaccines

      review-article
      Author(s): a , 1 , a , 1 , a , 1 , a , b , c , *
      Publication date (Electronic):
      Journal: Advanced Drug Delivery Reviews
      Publisher: Elsevier B.V.
      Keywords: mRNA delivery, Gene delivery, Lipid nanoparticles, Self-assembly, Immunization, COVID-19, ACE2, Angiotensin-converting enzyme 2, APC, Antigen-presenting cell, ApoE, Apolipoprotein E, ARCA, “Anti-reverse" cap analog, BCR, B-cell receptor, COVID-19, Coronavirus Disease 2019, Cryo-(T)EM, Cryogenic (transmission) electron microscopy, DC, Dendritic cell, DGTS, 1,2-Dipalmitoyl-sn-glycero-3-O-4'-(N,N,N-trimethyl)-homoserine, DLin-MC3-DMA, MC3, (6Z,9Z,28Z,31Z)-Heptatriacont-6,9,28,31-tetraene-19-yl 4-(dimethylamino)butanoate, DMG-PEG-2000, 1,2-Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000, DODMA, 1,2-Dioleyloxy-3-dimethylaminopropane, DOGS, N1,N1'-(8-(dioctadecylamino)-5,8-dioxooctane-1,4-diyl)bis(propane-1,3-diaminium), DOPE, 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine, DOTAP, 1,2-Dioleoyl-3-trimethylammonium-propane, DOTMA, 1,2-Di-O-octadecenyl-3-trimethylammonium propane, DSPC, 1,2-Distearoyl-sn-glycero-3-phosphocholine, EUA, Emergency Use Authorization, GMP, Good manufacturing practice, GC, Germinal center, HIV, Human immunodeficiency virus, HPLC, High-performance liquid chromatography, ID, Intradermal, IgA, IgG, Immunoglobulin A, G, IL, Ionizable lipid, IM, Intramuscular, IV, Intravenous, IVT, In vitro transcription, LN, Lymph node, LNP, Lipid nanoparticle, MHC, Major histocompatibility complex, mRNA, Messenger RNA, PBAE, Poly(beta-amino esters), pDNA, Plasmid DNA, PEG, Poly(ethylene glycol), PEI, Poly(ethylene imine), PET-CT, Positron emission tomography- computed tomography, PLGA, Poly(lactic-co-glycolic acid), RBD, Receptor Binding Domain, RSV, Respiratory syncytial virus, SAR, Structure-activity relationship, saRNA, Self-amplifying RNA, SARS-CoV-2, Severe acute respiratory syndrome coronavirus-2, SAXS, Small-angle X-ray scattering, SC, Subcutaneous, siRNA, Small interfering RNA, TLR, Toll-like receptor, TH1, Type 1 T helper cell, UTR, Untranslated region

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          mRNA vaccines have evolved from being a mere curiosity to emerging as COVID-19 vaccine front-runners. Recent advancements in the field of RNA technology, vaccinology, and nanotechnology have generated interest in delivering safe and effective mRNA therapeutics. In this review, we discuss design and self-assembly of mRNA vaccines. Self-assembly, a spontaneous organization of individual molecules, allows for design of nanoparticles with customizable properties. We highlight the materials commonly utilized to deliver mRNA, their physicochemical characteristics, and other relevant considerations, such as mRNA optimization, routes of administration, cellular fate, and immune activation, that are important for successful mRNA vaccination. We also examine the COVID-19 mRNA vaccines currently in clinical trials. mRNA vaccines are ready for the clinic, showing tremendous promise in the COVID-19 vaccine race, and have pushed the boundaries of gene therapy.

          Graphical abstract

          Highlights

          • •

            mRNA vaccines showed spectacular success in the race for COVID-19 vaccines.

          • •

            Design of both mRNA and the delivery vectors help in fine-tuning efficacy.

          • •

            Self-assembled mRNA delivery vectors include lipid and polymer nanoparticles.

          • •

            Lipid nanoparticle mRNA vaccines have ca. 95% efficacy and earned EUA FDA approval.

          • •

            These unprecedented results may pave the road for future mRNA vaccine development.

          Related collections

          Most cited references301

          • Record: found
          • Abstract: found
          • Article: not found

          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
          Article 0 comments Cited 21932 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Clinical Characteristics of Coronavirus Disease 2019 in China

            Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
            Article 0 comments Cited 13613 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found

              Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

              Dawei Wang, Bo Hu, Fangfang Zhu … (2020)
              In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
              Article 0 comments Cited 10841 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Adv Drug Deliv Rev
                Journal ID (iso-abbrev): Adv Drug Deliv Rev
                Title: Advanced Drug Delivery Reviews
                Publisher: Elsevier B.V.
                ISSN (Print): 0169-409X
                ISSN (Electronic): 1872-8294
                Publication date PMC-release: 2 January 2021
                Publication date (Print): March 2021
                Publication date (Electronic): 2 January 2021
                Volume: 170
                Pages: 83-112
                Affiliations
                [a ]Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Robertson Life Science Building, 2730 South Moody Avenue, Portland, Oregon 97201, USA
                [b ]Department of Biomedical Engineering, Oregon Health & Science University, Robertson Life Science Building, 2730 South Moody Avenue, Portland, Oregon 97201, USA
                [c ]Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97239, USA
                Author notes
                [* ]Corresponding author at: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Robertson Life Science Building, 2730 South Moody Avenue, Portland, Oregon 97201, USA.
                [1]

                These authors contributed equally to the work.

                Article
                Publisher Item ID: S0169-409X(20)30293-3
                DOI: 10.1016/j.addr.2020.12.014
                PMC ID: 7837307
                PubMed ID: 33400957
                SO-VID: c9ea17e4-37dd-40f5-96fd-0f97818ec22f
                Copyright © © 2020 Elsevier B.V. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 1 November 2020
                Date revision received : 22 December 2020
                Date accepted : 27 December 2020
                Categories
                Subject: Article

                Keywords: mrna delivery,gene delivery,lipid nanoparticles,self-assembly,immunization,covid-19,ace2, angiotensin-converting enzyme 2,apc, antigen-presenting cell,apoe, apolipoprotein e,arca, “anti-reverse" cap analog,bcr, b-cell receptor,covid-19, coronavirus disease 2019,cryo-(t)em, cryogenic (transmission) electron microscopy,dc, dendritic cell,dgts, 1,2-dipalmitoyl-sn-glycero-3-o-4'-(n,n,n-trimethyl)-homoserine,dlin-mc3-dma, mc3, (6z,9z,28z,31z)-heptatriacont-6,9,28,31-tetraene-19-yl 4-(dimethylamino)butanoate,dmg-peg-2000, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000,dodma, 1,2-dioleyloxy-3-dimethylaminopropane,dogs, n1,n1'-(8-(dioctadecylamino)-5,8-dioxooctane-1,4-diyl)bis(propane-1,3-diaminium),dope, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine,dotap, 1,2-dioleoyl-3-trimethylammonium-propane,dotma, 1,2-di-o-octadecenyl-3-trimethylammonium propane,dspc, 1,2-distearoyl-sn-glycero-3-phosphocholine,eua, emergency use authorization,gmp, good manufacturing practice,gc, germinal center,hiv, human immunodeficiency virus,hplc, high-performance liquid chromatography,id, intradermal,iga, igg, immunoglobulin a, g,il, ionizable lipid,im, intramuscular,iv, intravenous,ivt, in vitro transcription,ln, lymph node,lnp, lipid nanoparticle,mhc, major histocompatibility complex,mrna, messenger rna,pbae, poly(beta-amino esters),pdna, plasmid dna,peg, poly(ethylene glycol),pei, poly(ethylene imine),pet-ct, positron emission tomography- computed tomography,plga, poly(lactic-co-glycolic acid),rbd, receptor binding domain,rsv, respiratory syncytial virus,sar, structure-activity relationship,sarna, self-amplifying rna,sars-cov-2, severe acute respiratory syndrome coronavirus-2,saxs, small-angle x-ray scattering,sc, subcutaneous,sirna, small interfering rna,tlr, toll-like receptor,th1, type 1 t helper cell,utr, untranslated region
                Data availability:
                Keywords: mrna delivery, gene delivery, lipid nanoparticles, self-assembly, immunization, covid-19, ace2, angiotensin-converting enzyme 2, apc, antigen-presenting cell, apoe, apolipoprotein e, arca, “anti-reverse" cap analog, bcr, b-cell receptor, covid-19, coronavirus disease 2019, cryo-(t)em, cryogenic (transmission) electron microscopy, dc, dendritic cell, dgts, 1,2-dipalmitoyl-sn-glycero-3-o-4'-(n,n,n-trimethyl)-homoserine, dlin-mc3-dma, mc3, (6z,9z,28z,31z)-heptatriacont-6,9,28,31-tetraene-19-yl 4-(dimethylamino)butanoate, dmg-peg-2000, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000, dodma, 1,2-dioleyloxy-3-dimethylaminopropane, dogs, n1,n1'-(8-(dioctadecylamino)-5,8-dioxooctane-1,4-diyl)bis(propane-1,3-diaminium), dope, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, dotap, 1,2-dioleoyl-3-trimethylammonium-propane, dotma, 1,2-di-o-octadecenyl-3-trimethylammonium propane, dspc, 1,2-distearoyl-sn-glycero-3-phosphocholine, eua, emergency use authorization, gmp, good manufacturing practice, gc, germinal center, hiv, human immunodeficiency virus, hplc, high-performance liquid chromatography, id, intradermal, iga, igg, immunoglobulin a, g, il, ionizable lipid, im, intramuscular, iv, intravenous, ivt, in vitro transcription, ln, lymph node, lnp, lipid nanoparticle, mhc, major histocompatibility complex, mrna, messenger rna, pbae, poly(beta-amino esters), pdna, plasmid dna, peg, poly(ethylene glycol), pei, poly(ethylene imine), pet-ct, positron emission tomography- computed tomography, plga, poly(lactic-co-glycolic acid), rbd, receptor binding domain, rsv, respiratory syncytial virus, sar, structure-activity relationship, sarna, self-amplifying rna, sars-cov-2, severe acute respiratory syndrome coronavirus-2, saxs, small-angle x-ray scattering, sc, subcutaneous, sirna, small interfering rna, tlr, toll-like receptor, th1, type 1 t helper cell, utr, untranslated region

                Comments

                Comment on this article

                scite_

                Similar content507

                See all similar

                Cited by123

                See all cited by

                Most referenced authors6,932

                See all reference authors