Table 1.
Examples of synthetic modified mRNAs for therapeutic applications. LNP, lipid nanoparticle; CNE, cationic nanoemulsion; DENV, dengue virus; prM-E, premembrane and envelope glycoproteins; CAR, chimeric antigen receptors; IL-22BP, interleukin-22 binding protein; VSVMP, vesicular stomatitis virus matrix protein; MUC1, tumor-associated antigens mucin 1; CEA, carcinoembryonic; HER2, human epidermal growth factor receptor 2; MAA, melanoma-associated antigen; VEGF-A, vascular endothelial growth factor-A; CCR5, human C-C chemokine receptor 5; TALENs, transcription activator-like effector nucleases; PKLR, pyruvate kinase L/R gene; Cpf1, CRISPR from Prevotella and Francisella 1.
| Modification type | Delivery system/Method | mRNA encoding | Application | Year | Refs | ||
|---|---|---|---|---|---|---|---|
| m1Ψ | LNP | Spike protein | Infectious disease vaccines | COVID-19 | mRNA-1273 | 2020 | [[157], [160]] |
| m1Ψ | LNP | Spike protein | BNT162 | 2020 | [[159], [161]] | ||
| Unknown | LNP | Spike protein | ARCoV | 2020 | [162] | ||
| m1Ψ | LNP | Haemagglutinin | Influenza | 2019 | [[151], [165]] | ||
| m1Ψ | LNP | Structural proteins | DENV | 2020 | [167] | ||
| m1Ψ | LNP | Glycoproteins C, D, and E | HSV-2 | 2019 | [169,170] | ||
| Unknown | CNE | Glycoprotein G | Rabies | 2020 | [171] | ||
| m1Ψ | LNP | prM-E protein | ZIKV | 2017 | [113,168] | ||
| m1Ψ | LNP | Envelope | HIV-1 | 2019 | [172,173] | ||
| Unknown | T cells transfected ex vivo | CAR-HER2 | Cancer immunotherapy | Glioblastoma | 2013 | [179] | |
| Unknown | T cells transfected ex vivo | CAR-CD19 | Leukemia | 2011 | [180] | ||
| Unknown | DCs transfected ex vivo | IL-22BP; VSVMP | Colon cancer | 2018 | [181,182] | ||
| Unknown | LNP | MUC1, CEA, HER2 etc. | Renal cell cancer | 2011 | [183] | ||
| Unknown | DCs transfected ex vivo | MAA | Melanoma | 2013 | [177] | ||
| Ψ; m5C | Transfection ex vivo | Yamanaka factors | Genetic reprogramming and protein-replacement | Generating iPSCs | 2010 | [64] | |
| Unknown | Transfection ex vivo | VEGF-A | Differentiation from iPSCs | 2016 | [189] | ||
| Unknown | DCs transfected ex vivo | IL-4 | Autoimmune diabetes | 2010 | [190] | ||
| Unknown | Transfected ex vivo | IL-10 | Autoimmune myocarditis | 2012 | [191] | ||
| s2U; m5C | LNP | Surfactant protein B | Congenital lung disease | 2011 | [66] | ||
| Unknown | Transfection ex vivo | VEGF-A | Heart failure | 2020 | [29] | ||
| Unknown | Transfection ex vivo | Cas9 nuclease | mRNA-based gene editing | Editing CAR T cells | 2017 | [194] | |
| Ψ | Transfection ex vivo | Cas9 nuclease | Editing CAR T cells | 2018 | [195] | ||
| Unknown | Transfection ex vivo | Zinc-finger nucleases | Engineering animal models | 2009 | [201] | ||
| Unknown | Transfection ex vivo | Zinc-finger nucleases | Editing HIV-1 CCR5 gene | 2017 | [29] | ||
| Unknown | Transfection ex vivo | TALEN | Editing PKLR gene | 2019 | [203] | ||
| Unknown | Transfection ex vivo | Cpf1 | Engineering animal models | 2016 | [204] | ||