Cell reportsSep 7, 2026

Fixing a human disease trait through mRNA transfer between cells

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 8, 2026

Abstract

Transferred mRNAs can undergo translation and potentially restore cellular functions in mutant cells.

Intercellular transfer of mRNAs occurs through tunneling nanotubes (TNTs).
Transferred mRNAs can complement genetic mutations, as shown in vitro with Zellweger Syndrome models.
Co-culture of mutant fibroblasts with wild-type cells results in de novo peroxisome biogenesis.
Genetic complementation was also observed with mRNAs encoding specific transcription factors.
Complementation is mediated by TNT transfer and translation, not by exosomes or protein transfer.

Simplified

There is growing evidence that mRNAs undergo intercellular transfer through cytoplasmic connections called tunneling nanotubes (TNTs), but whether transferred mRNAs are translated and affect cellular changes post-transfer is unknown. Using multiple lines of evidence, we show that transferred mRNAs undergo translation and can complement the phenotype of genetic mutations in vitro. For example, the human peroxisome biogenesis disorder, Zellweger Syndrome, results from mutations in genes such as PEX5 and PEX6. We demonstrate that the co-culture of patient-derived PEX6 mutant fibroblasts or PEX5 knockout cells with wild-type cells leads to de novo peroxisome biogenesis. We provide additional examples of genetic complementation via transfer of mRNAs encoding the HSF1 transcription factor or CRE recombinase. Complementation occurs by TNT-mediated mRNA transfer and translation in acceptor cells, but not by exosomes, nor by protein or peroxisome transfer. Our study provides evidence for the physiological significance of mRNA transfer and suggests another approach for mRNA therapeutics.

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Fixing a human disease trait through mRNA transfer between cells

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