Engineering mRNA for Personalized Medicine

Engineered mRNA transforms cells into tiny bio-factories, producing drugs that treat inflammatory skin diseases and cancers. This technology paves the way for personalized medicine, where the body makes its own drugs.

mRNA, familiar from COVID-19 vaccines, directs cells to make specific proteins. Researchers at the University of Texas used engineered mRNA to prompt cells to secrete therapeutic proteins, successfully treating psoriasis and cancer in mice.

Daniel Siegwart, a professor at UT Southwestern, envisions a future where patients receive monthly treatments at home, improving their quality of life.

The study introduced a novel approach: using engineered signal peptides (SPs) to guide proteins out of cells for systemic therapeutic effects. SPs act as metaphorical transport labels, directing proteins to their destinations within or outside the cell.

Researchers modified mRNA to include a secretion-oriented SP, then attached it to mRNA sequences encoding various proteins, including therapeutic ones like etanercept and anti-PD-L1.

When delivered via lipid nanoparticles, these modified mRNAs caused cells to secrete the encoded proteins into the extracellular fluid. In mice, this treatment reduced psoriatic skin patches and slowed tumor growth, doubling survival rates.

This technique, dubbed Signal Peptide-Engineered Nucleic Acid Design (SEND), could enhance the efficacy of protein drugs currently delivered by infusion, reducing side effects. It promises to improve health and quality of life for patients with inflammatory diseases, cancers, blood clotting disorders, diabetes, and genetic conditions.

The study was published in the Proceedings of the National Academy of Sciences (PNAS).