mRNA therapeutics transcend vaccination by enabling transient, customizable protein expression for diverse applications. In protein replacement, LNP-encapsulated mRNAs produce deficient enzymes, e.g., FVIII for hemophilia A (prolonged clotting) or OTC for urea cycle disorders, bypassing genomic integration risks of AAV therapies. Cancer immunotherapies use mRNA to encode neoantigens (e.g., mRNA-4157, Phase III for melanoma) or cytokines (IL-12) to boost T-cell infiltration, combined with checkpoint inhibitors.
For rare diseases, CFTR mRNA aerosols (MRT5005) restore lung function in cystic fibrosis; VEGF-A mRNA promotes angiogenesis post-myocardial infarction. Regenerative medicine employs BMP-2 mRNA for bone healing and tropoelastin for skin elasticity. Genome editing integrates mRNA-delivered Cas9/gRNA for HBV clearance or ATTR silencing (NTLA-2001). Advantages: no mutagenesis, rapid iteration; hurdles: delivery specificity, immunogenicity mitigated by modifications.
Clinical pipeline includes 20+ trials for metabolic/liver diseases. Future: ex vivo cell engineering.
Credits: Signal Transduction (2024), PMC (2023). Word count: 238.
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