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Synthetic RNA “Nanostars” Create Programmable Compartments in Bacteria

Source: Press release written by the Department of Chemical Engineering and Biotechnology, University of Cambridge

Researchers have found a new way to organise molecules inside living cells, opening possibilities for more controlled and efficient biomanufacturing.

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Lorenzo Di Michele

A team led by Lorenzo Di Michele (University of Cambridge, UK), in collaboration with Graham Christie (University of Cambridge, UK), Pietro Cicuta (University of Cambridge, UK), and Masahiro Takinoue (Institute of Science Tokyo, Japan) has demonstrated that engineered RNA molecules can self-assemble into membraneless organelles inside Escherichia coli (E. coli). Their findings were published in Nature Communications in February 2026.

These structures create compartmentalised environments that bacteria do not naturally possess, allowing specific molecules and proteins to be concentrated and manipulated within the cell.

Such control over cellular organisation could support improved production and purification of synthetic proteins used in therapeutics and biotechnology research.

The researchers designed four-armed RNA “nanostars” that assemble through programmed base-pairing interactions. When expressed in E. coli, these engineered RNAs formed condensates resembling membraneless organelles. Using fluorescence, the team showed that the structures assembled and dissolved in response to temperature changes, demonstrating predictable and reversible behaviour consistent with phase separation.

Crucially, when one arm of the nanostar carried an aptamer – an RNA sequence designed to selectively capture proteins – fluorescent proteins were concentrated within the organelles inside the bacterial cells.

“This is about using RNA nanotechnology to engineer synthetic organelles in bacteria that wouldn’t otherwise have them,” said Di Michele.

“This could be very useful for biomanufacturing applications, including production and purification of synthetic proteins useful in all sorts of fields, from therapeutics to biotech research.”

The paper, Expression of nano-engineered RNA organelles in bacteria, comes from joint first authors Brian Ng, Catherine Fan, Milan Dordevic, Adam Knirsch of Di Michele’s DNA Nanotechnology research group in the Department of Chemical Engineering and Biotechnology at the University of Cambridge (UK).