AI Article Synopsis
- Loss of elastin due to aging or injury can negatively impact tissue function, prompting a study on tropoelastin (TE) synthesis using synthetic mRNA variants.
- Codon optimization effectively enhances protein synthesis without harming cell viability, while nucleotide modifications reduce toxicity.
- The study successfully demonstrates that certain mRNA variants can significantly increase TE protein expression in porcine skin, with no observed toxicity, highlighting the potential for synthetic mRNA in enhancing tissue repair.
Article Abstract
Loss of elastin due to aging, disease, or injury can lead to impaired tissue function. In this study, tropoelastin (TE) synthesis is investigated and using different TE-encoding synthetic mRNA variants after codon optimization and nucleotide modification. Codon optimization shows a strong effect on protein synthesis without affecting cell viability , whereas nucleotide modifications strongly modulate translation and reduce cell toxicity. Selected TE mRNA variants (3, 10, and 30 μg) are then analyzed in porcine skin after intradermal application. Administration of 30 μg of native TE mRNA with a me Ψ modification or 10 and 30 μg of unmodified codon-optimized TE mRNA is required to increase TE protein expression . In contrast, just 3 μg of a codon-optimized TE mRNA variant with the me Ψ modification is able to increase protein expression. Furthermore, skin toxicity is investigated by injecting 30 μg of mRNA of selected TE mRNA variants into a human full-thickness skin model, and no toxic effects are observed. Thereby, for the first time, an increased dermal TE synthesis by exogenous administration of synthetic mRNA is demonstrated . Codon optimization of a synthetic mRNA can significantly increase protein expression and therapeutic outcome.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462787 | PMC |
| http://dx.doi.org/10.1016/j.omtn.2023.07.035 | DOI Listing |
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