Improved tropoelastin synthesis in the skin by codon optimization and nucleotide modification of tropoelastin-encoding synthetic mRNA.

ABSTRACT: Loss of elastin due to aging, disease, or injury can lead to impaired tissue function. In this study, de novo tropoelastin (TE) synthesis is investigated in vitro and in vivo 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 in vitro, whereas nucleotide modifications strongly modulate translation and reduce cell toxicity. Selected TE mRNA variants (3, 10, and 30 μg) are then analyzed in vivo in porcine skin after intradermal application. Administration of 30 μg of native TE mRNA with a me¹ Ψ modification or 10 and 30 μg of unmodified codon-optimized TE mRNA is required to increase TE protein expr

SUBMITTER: Golombek S 

PROVIDER: S-EPMC10462787 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature