RNA exporters enable nondestructive cell monitoring, delivery of therapeutics

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RNA exporters could enable the nondestructive monitoring of cells over time and the targeted delivery of mRNA therapeutics, according to a paper published recently in Cell.

The technology, which was developed by a team at the California Institute of Technology (Caltech), addresses two seemingly independent challenges. First, the system enables the monitoring of changes in cells over time by packaging RNA molecules into protective nanoparticles. Once secreted from the cell, the RNA can be sequenced to generate insights into what is happening inside the cell.

Second, the technology allows researchers to use the nanoparticles to deliver genetic material into cells. The leading COVID-19 vaccines already deliver genetic material, mRNA, into cells to trigger the production of a protein that helps the immune system detect and destroy SARS-CoV-2. However, the lipid nanoparticles used to deliver the mRNA COVID-19 vaccine cannot target specific cells, rendering them unsuitable for treating diseases that affect particular parts of the body.

Michael Elowitz, co-author of the paper and professor of biology and bioengineering at Caltech, explained how the RNA export technology, COURIER, provides a foundation for the cell-to-cell delivery of RNA.

“Living cells could, in principle, operate as programmable mRNA delivery vehicles that bring therapeutic mRNA to the right cells in the right places in the body. To achieve that vision, we need a way to export specific mRNAs in a format that can be taken up and expressed by other cells. That is what this system provides. COURIER allows one cell to produce mRNA and then encapsulate it in particles that deliver it to other cells, which then express it,” Elowitz said in a statement.

In cell monitoring, the same system is used for a different purpose. Researchers currently need to kill cells to access internal molecules that reveal insights about how they change over time, such as in embryonic development and aging. COURIER could enable researchers to access RNA without killing cells and thereby facilitate monitoring changes over time.

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