In a possible step forward for gene therapy, Stanford researchers made mice glow like fireflies

A collaboration between chemists and gene therapy experts produced a new way of inserting the code for modified proteins into the cells of mice. If successful in humans, the technique could be useful for vaccines or cancer therapies.

Timothy Blake, a postdoctoral fellow in the Waymouth lab, was hard at work on a fantastical interdisciplinary experiment. He and his fellow researchers were refining compounds that would carry instructions for assembling the protein that makes fireflies light up and deliver them into the cells of an anesthetized mouse. If their technique worked, the mouse would glow in the dark.

Not only did the mouse glow, but it also later woke up and ran around, completely unaware of the complex series of events that had just taken place within its body. Blake said it was the most exciting day of his life.

This success, the topic of a recent paper in Proceedings of the National Academy of Sciences, could mark a significant step forward for gene therapy. It’s hard enough getting these protein instructions, called messenger RNA (mRNA), physically into a cell. It’s another hurdle altogether for the cell to actually use them to make a protein. If the technique works in people, it could provide a new way of inserting therapeutic proteins into diseased cells.

Although the results are impressive, this technique is remarkably simple and fast. And unlike traditional gene therapy that permanently alters the genetic makeup of the cell, mRNA is short-lived and its effects are temporary. The transient nature of mRNA transmission opens up special opportunities, such as using these compounds for vaccination or cancer immunotherapy.

This research was made possible through coordination between the chemists and experts in imaging molecules in live animals, who rarely work together directly. With this partnership, the synthesis, characterization and testing of compounds could take as little as a week.

Additional co-authors of this study, “Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals,” include Timothy Blake, Colin McKinlay, Jessica Vargas, Jonathan Hardy, Masamitsu Kanada and Christopher Contag. Waymouth is a professor, by courtesy, of chemical engineering, a member of Stanford Bio-X, a faculty fellow of Stanford ChEM-H and an affiliate of the Stanford Woods Institute for the Environment. Wender is a professor, by courtesy, of chemical and systems biology, a member of Stanford Bio-X, a member of the Stanford Cancer Institute and a faculty fellow of Stanford ChEM-H. Contag is a professor, by courtesy, of radiology and of bioengineering, a member of Stanford Bio-X, a member of the Child Health Research Institute and a member of the Stanford Cancer Institute.

This work was funded by the Department of Energy, the National Science Foundation, the National Institutes of Health, the Chambers Family Foundation for Excellence in Pediatric Research, the Child Health Research Institute, the Stanford Center for Molecular Analysis and Design and the National Center for Research Resources.