Delivery of messenger RNA (mRNA) into living cells, followed by expression of encoded proteins, has potential applications in protein replacement therapy and vaccination. However, the design and implementation of a chemically accessible, efficacious, and safe system for mRNA delivery remain challenging.
Researchers developed a system that consists of compounds called charge-altering releasable transporters (CARTs). The positively charged CARTs bind to negatively charged mRNAs for delivery into cells, whereupon the CARTs undergo an intramolecular rearrangement that neutralizes the positive charge, releasing the mRNAs.
The authors synthesized CARTs of varying lengths and compositions using a relatively rapid two-step process. When cultured human cells were treated with a CART/mRNA complex encoding enhanced green fluorescent protein, more than 99% of cells exhibited detectable fluorescence.
Both intramuscular and intravenous injection of CART/mRNA complexes encoding the luminescent protein luciferase into mice led to high levels of luciferase expression that persisted for 24 hours or longer.
According to the authors, CART-mediated mRNA delivery might have a broad range of research and therapeutic applications.
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