Unlocking the Potential of Gap Junctions to Advance Drug Delivery

gap junctions to transport therapeutics

Researchers propose using channels embedded in plasma membranes of adjacent cells, known as the gap junction network (in green), as passageways for delivery of RNA interference therapeutics.

Assistant Professor Jeanne Stachowiak of the Department of Biomedical Engineering and Associate Professor Hugh Smyth from the College of Pharmacy have received a new grant from the National Institutes of Health to advance sophisticated siRNA drug delivery.

The ability of small interfering RNA (siRNA) to silence specific gene expression is one of the most promising discoveries in biomedical research over the last two decades. The ability of siRNA macromolecules to turn off certain gene behaviors could be a powerful tool in treating diseases such as cancer, which results when genes mutate uncontrollably.

However, there are challenges in delivering these RNA interference therapeutics to disease sites. One hurdle is that the therapeutics are unable to permeate across cell membrane barriers. The therapeutics also degrade rapidly and lose their effectiveness in the extracellular matrix. Conventional methods to address these challenges have included encapsulating RNA interference therapeutics in protective nanoparticles. However, nanoparticles have been too toxic to work effectively.

Stachowiak and Smyth propose using the cellular architecture itself to deliver these potent therapeutics. Specifically in this study, the team will use the cellular gap junction network to transport powerful siRNA.

This network includes the channels embedded in the plasma membranes of adjacent cells that come together to form gap junctions, or direct passageways between the cytoplasm of a cell and its neighbors.

"What makes this work exciting is that it explores a new route for delivering small interfering RNA into the cellular interior," says Jeanne Stachowiak. "A lot of previous work has focused on disrupting cell membranes, but our work is the first to ask whether the gap junction network can be harnessed for gene silencing."

In her previous research, Stachowiak used the gap junction network to develop a novel drug delivery system called the connectosome. The system has successfully delivered chemotherapy directly to individual cells more effectively than conventional liposomal delivery. Based off of that preliminary work, the next phase of research will focus on how the gap junction network can more efficiently deliver siRNA therapeutics.

The research team will study this method in breast cancer models with the goals of increasing the efficiency and reducing the toxicity of siRNA therapeutics to unlock their potential for treating diverse diseases.

Learn more about connectosomes and the foundational research for this upcoming study.