mRNA in the Context of Protein Replacement Therapy
Abstract
:1. Introduction
Protein Replacement Options—Why Choose mRNA?
2. Considerations on mRNA Production for Protein Replacement Therapies
mRNA Architecture for Successful Protein Production
3. Vehicles for Delivering mRNA to the Cells
4. Critical Quality Attributes for mRNA-Based Protein Replacement Therapies
5. mRNA-Based Protein Replacement Therapies in Preclinical and Clinical Stage
6. Conclusions and Future Applications
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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NCT NUMBER/PHASE | CONDITION | DELIVERY SYSTEM | ENCODING SEQUENCE/PROTEIN MOLECULAR WEIGHT | SUBJECTS | INTERVENTION | STATUS |
---|---|---|---|---|---|---|
NCT03370887/Phase II | Heart failure | Naked mRNA | VEGF-A 27 kDa [126] | Twenty-four patients with compromised left ventricular function that undergo surgical revascularization. | Patients had received either AZD8601 or placebo as epicardial injections and were followed up for six months. | Completed |
NCT02935712/Phase I | Male subjects with type II diabetes | Naked mRNA | VEGF-A 27 kDa [126] | Up to sixty male patients with type II diabetes, aged 18–65 years old | In Part A, subjects had received an intradermal injection (ID) of either AZD8601 or placebo in a single ascending dose. In Part B, patients had received an ID injection of either AZD8601, in forearm skin, or the placebo. | Completed |
NCT04159103/Phase I/II | Propionic Acidemia (PA) | LNPs | Alpha and Beta subunits of propionyl-CoA carboxylaseAlpha chain: 72 kDa Beta chain: 56 kDA [127] | Thirty-six patients with genetically confirmed PA, from one year old and older. | In Phase I, the patients will receive doses of mRNA-3927, for the dose optimization stage and subsequently for the dose expansion stage. In Phase II, the patients will receive the identified intravenous dose of mRNA-3927 and will be followed up for two years. | Recruiting |
NCT03810690/Phase I/II | Methylmalonic acidemia (MMA) | LNPs | Methylmalonyl-coenzyme A mutase (MUT) 78 kDa [128] | Patients with methylmalonic academia, aged 1–18 years old, with elevated plasma methylmalonic acid. | The patients were about to receive doses of mRNA-3704, for the dose escalation phase, and subsequently for the dose expansion stage. | Withdrawn |
NCT03767270/Phase I/II | Ornithine transcarbamylase deficiency (OTCD) | LNPs | Ornithine transcarbamylase 36.1 kDa [129] | Subjects with OTC Deficiency | The patients were about to receive intravenous, single-ascending low, mid and high doses of MRT5201 or the placebo. | Withdrawn |
NCT03375047/Phase I/II | Cystic fibrosis (CF) | LNPs | Human cystic fibrosis transmembrane regulator protein (CFTR) 127 kDa [130] | Forty adult subjects with CF | The patients are supposed to receive single and multiple escalating doses of MRT5005, administered by nebulization to the respiratory tract, or the placebo. | Unknown |
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Vavilis, T.; Stamoula, E.; Ainatzoglou, A.; Sachinidis, A.; Lamprinou, M.; Dardalas, I.; Vizirianakis, I.S. mRNA in the Context of Protein Replacement Therapy. Pharmaceutics 2023, 15, 166. https://doi.org/10.3390/pharmaceutics15010166
Vavilis T, Stamoula E, Ainatzoglou A, Sachinidis A, Lamprinou M, Dardalas I, Vizirianakis IS. mRNA in the Context of Protein Replacement Therapy. Pharmaceutics. 2023; 15(1):166. https://doi.org/10.3390/pharmaceutics15010166
Chicago/Turabian StyleVavilis, Theofanis, Eleni Stamoula, Alexandra Ainatzoglou, Athanasios Sachinidis, Malamatenia Lamprinou, Ioannis Dardalas, and Ioannis S. Vizirianakis. 2023. "mRNA in the Context of Protein Replacement Therapy" Pharmaceutics 15, no. 1: 166. https://doi.org/10.3390/pharmaceutics15010166
APA StyleVavilis, T., Stamoula, E., Ainatzoglou, A., Sachinidis, A., Lamprinou, M., Dardalas, I., & Vizirianakis, I. S. (2023). mRNA in the Context of Protein Replacement Therapy. Pharmaceutics, 15(1), 166. https://doi.org/10.3390/pharmaceutics15010166