MIT Researchers Turn Liver into mRNA Factory to Rejuvenate Aging Immune Systems

CAMBRIDGE, MA — December 19, 2025— In a breakthrough study published in Nature, researchers at MIT have unveiled a novel mRNA-based strategy to reverse age-related immune decline by transforming the liver into a temporary production hub for T-cell maturation factors.

As the human body ages, the thymus—the primary organ for T-cell development—undergoes involution, eventually becoming nonfunctional. This leads to a diminished T-cell repertoire, leaving the elderly highly susceptible to infections and less responsive to vaccines. To bypass this “thymic collapse,” a team led by Feng Zhang at the McGovern Institute for Brain Research utilized mRNA technology to reprogram hepatocytes to secrete the critical signaling proteins typically produced by a youthful thymus.

The Liver as a Synthetic mRNA Factory

The researchers selected the liver as their target for mRNA delivery due to the organ’s high protein-synthetic capacity and its high accessibility for lipid nanoparticle (LNP)-mediated mRNA uptake. By delivering a specific mRNA cocktail encoding three key factors—DLL1, FLT-3, and IL-7—the team successfully engineered the liver to mimic the biochemical environment of a functional thymus.

“Our approach is a synthetic one,” explains senior author Feng Zhang. “We are using mRNA to engineer the body to mimic thymic factor secretion, effectively restoring essential immune protection.”

Proven Efficacy via mRNA Delivery

In preclinical trials involving 18-month-old mice (equivalent to humans in their 50s), the mRNA treatment yielded significant immunological gains:

• Vaccination Response: Aged mice receiving the mRNA treatment showed a 100% increase in cytotoxic T-cell populations following vaccination compared to untreated controls.

• Cancer Immunotherapy: Mice treated with the mRNA cocktail alongside PD-L1 checkpoint inhibitors demonstrated significantly higher survival rates, proving that mRNA can revitalize the T-cell response against tumors.

• T-Cell Diversity: The mRNA-driven production of factors from the liver fostered a larger and more diverse T-cell repertoire, compensating for the lack of new cell production in the aged thymus.

The Future of mRNA-Based Immunotherapy

Because mRNA is transient, the researchers noted that the treatment allows for precise, temporary control over protein production without the long-term side effects associated with systemic growth factor injections. Lead author Mirco Friedrich emphasizes that this mRNA platform could eventually help elderly patients lead healthier lives by maintaining immune vigilance.

Following this success, the team plans to further optimize the mRNA sequences and explore whether additional factors encoded in the mRNA can enhance B-cell function and broader immune health.