The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics
Advances in molecular biology have revolutionized the use of messenger RNA (mRNA) as a therapeutic. The concept of nucleic acid therapy with mRNA originated in 1990 when Wolff et al. reported successful expression of proteins in target organs by direct injection of either plasmid DNA or mRNA. It too...
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| Format: | Article |
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14820 |
| _version_ | 1797575762174279680 |
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| author | Albert Muslimov Valeriy Tereshchenko Daniil Shevyrev Anna Rogova Kirill Lepik Vasiliy Reshetnikov Roman Ivanov |
| author_facet | Albert Muslimov Valeriy Tereshchenko Daniil Shevyrev Anna Rogova Kirill Lepik Vasiliy Reshetnikov Roman Ivanov |
| author_sort | Albert Muslimov |
| collection | DOAJ |
| description | Advances in molecular biology have revolutionized the use of messenger RNA (mRNA) as a therapeutic. The concept of nucleic acid therapy with mRNA originated in 1990 when Wolff et al. reported successful expression of proteins in target organs by direct injection of either plasmid DNA or mRNA. It took decades to bring the transfection efficiency of mRNA closer to that of DNA. The next few decades were dedicated to turning in vitro-transcribed (IVT) mRNA from a promising delivery tool for gene therapy into a full-blown therapeutic modality, which changed the biotech market rapidly. Hundreds of clinical trials are currently underway using mRNA for prophylaxis and therapy of infectious diseases and cancers, in regenerative medicine, and genome editing. The potential of IVT mRNA to induce an innate immune response favors its use for vaccination and immunotherapy. Nonetheless, in non-immunotherapy applications, the intrinsic immunostimulatory activity of mRNA directly hinders the desired therapeutic effect since it can seriously impair the target protein expression. Targeting the same innate immune factors can increase the effectiveness of mRNA therapeutics for some indications and decrease it for others, and vice versa. The review aims to present the innate immunity-related ‘barriers’ or ‘springboards’ that may affect the development of immunotherapies and non-immunotherapy applications of mRNA medicines. |
| first_indexed | 2024-03-10T21:42:55Z |
| format | Article |
| id | doaj.art-98d1e85e5c74465183a7772f1ded3e31 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:42:55Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-98d1e85e5c74465183a7772f1ded3e312023-11-19T14:31:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124191482010.3390/ijms241914820The Dual Role of the Innate Immune System in the Effectiveness of mRNA TherapeuticsAlbert Muslimov0Valeriy Tereshchenko1Daniil Shevyrev2Anna Rogova3Kirill Lepik4Vasiliy Reshetnikov5Roman Ivanov6Scientific Center for Translational Medicine, Sirius University of Science and Technology, Olympic Ave 1, 354340 Sirius, RussiaScientific Center for Translational Medicine, Sirius University of Science and Technology, Olympic Ave 1, 354340 Sirius, RussiaScientific Center for Translational Medicine, Sirius University of Science and Technology, Olympic Ave 1, 354340 Sirius, RussiaLaboratory of Nano- and Microencapsulation of Biologically Active Substances, Peter the Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, 195251 St. Petersburg, RussiaRM Gorbacheva Research Institute, Pavlov University, L’va Tolstogo 6-8, 197022 St. Petersburg, RussiaScientific Center for Translational Medicine, Sirius University of Science and Technology, Olympic Ave 1, 354340 Sirius, RussiaScientific Center for Translational Medicine, Sirius University of Science and Technology, Olympic Ave 1, 354340 Sirius, RussiaAdvances in molecular biology have revolutionized the use of messenger RNA (mRNA) as a therapeutic. The concept of nucleic acid therapy with mRNA originated in 1990 when Wolff et al. reported successful expression of proteins in target organs by direct injection of either plasmid DNA or mRNA. It took decades to bring the transfection efficiency of mRNA closer to that of DNA. The next few decades were dedicated to turning in vitro-transcribed (IVT) mRNA from a promising delivery tool for gene therapy into a full-blown therapeutic modality, which changed the biotech market rapidly. Hundreds of clinical trials are currently underway using mRNA for prophylaxis and therapy of infectious diseases and cancers, in regenerative medicine, and genome editing. The potential of IVT mRNA to induce an innate immune response favors its use for vaccination and immunotherapy. Nonetheless, in non-immunotherapy applications, the intrinsic immunostimulatory activity of mRNA directly hinders the desired therapeutic effect since it can seriously impair the target protein expression. Targeting the same innate immune factors can increase the effectiveness of mRNA therapeutics for some indications and decrease it for others, and vice versa. The review aims to present the innate immunity-related ‘barriers’ or ‘springboards’ that may affect the development of immunotherapies and non-immunotherapy applications of mRNA medicines.https://www.mdpi.com/1422-0067/24/19/14820mRNAinnate immunityNF-κBPAMPDAMPcGAS/STING |
| spellingShingle | Albert Muslimov Valeriy Tereshchenko Daniil Shevyrev Anna Rogova Kirill Lepik Vasiliy Reshetnikov Roman Ivanov The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics International Journal of Molecular Sciences mRNA innate immunity NF-κB PAMP DAMP cGAS/STING |
| title | The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics |
| title_full | The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics |
| title_fullStr | The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics |
| title_full_unstemmed | The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics |
| title_short | The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics |
| title_sort | dual role of the innate immune system in the effectiveness of mrna therapeutics |
| topic | mRNA innate immunity NF-κB PAMP DAMP cGAS/STING |
| url | https://www.mdpi.com/1422-0067/24/19/14820 |
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