Engineering Programmable Artificial Organelles

By Elena Shen;

Outreach Associate; The Lawrenceville School, NJ

Researchers from UCLA have developed a way to use RNA to build and program artificial organelles. The lead author of the study on this approach, Shiyi Li, stated, “We can control how and where these RNA droplets form and what they attract, effectively creating new, temporary rooms inside the cell furnished with selected molecular tools”. This method allows scientists to control the size, location, and function of these droplet-shaped chambers, potentially giving researchers more control over cellular processes.

The programmability of these organelles sets them apart from previous approaches. They are a type of artificial biomolecular condensate that are formed spontaneously as molecules come together and imitate cellular biomolecular condensates. Biomolecular condensates are tiny membraneless compartments found in eukaryotic cells that concentrate substances such as proteins and nucleic acids. They play a part in gene expression, metabolism, and diseases. Recently, scientists have begun to use artificial condensates to influence cell behavior. However, this new method utilizes RNA’s base-pairing to manipulate the organelle into forming in specific ways.

To build the condensates, researchers created short RNA structures that they termed “nanostars,” because they folded into star-like shapes. Each nanostar had three or more arms, at the end of which there were complementary sequences called “kissing loops” that bound together, connecting groups of nanostars and forming a condensate. The researchers could control the structure of these groups by using RNA’s predictable base-pairing rules. Traditional condensates created from proteins lack this ability, as the structures are much less predictable. Previous methods involving RNA required using engineered target RNA to control folding, but the newly developed approach eliminates this need.

In addition, they were able to control the location where the condensates formed by changing the number and length of the nanostar arms and their affinity for interactions with other molecules. Changing the location allows for much more control over cellular processes, as most reactions occur in specific sections of the cell. This technology creates opportunities for scientists to develop synthetic organelles with specialized functions, and the UCLA Technology Development Group has applied for a patent related to the method.

Artificial biomolecular condensates are emerging as a powerful tool in manipulating cellular processes. For example, condensates are able to restrict the accumulation of viruses in cells. In June 2025, researchers engineered condensates that targeted tobacco mosaic viruses they had tagged. They were able to decrease the amount of viruses by over ten times as much as without the condensates, demonstrating the potential of these engineered organelles in agriculture and medicine. The method developed by UCLA researchers allows for easier and further specialization of these condensates, opening up many possibilities in the fields of nanomedicine, genetics, and cell engineering that are just beginning to be explored.

Works Cited

Baruch Leshem, A., Gaash, D. & Lampel, A. Design and applications of synthetic biomolecular condensates. Nat. Nanotechnol. 21, 39–52 (2026). https://doi.org/10.1038/s41565-025-02053-5

Li, S., Kim, Y., Wang, K. et al. Programmable artificial RNA condensates in mammalian cells. Nat. Nanotechnol. (2026). https://doi.org/10.1038/s41565-026-02164-7

Stanfield, A. M., & May, J. P. (2025). Engineered biomolecular condensates limit tobacco mosaic virus accumulation and symptom development. Molecular Plant Pathology, 26(6), 9. doi:https://doi-org.bunnlibrary.idm.oclc.org/10.1111/mpp.70113

Verwiel, M. A. M., Erkamp, N. A., & Hest, J. C. M. v. (2025). Converging frontiers in biomolecular condensate and synthetic cell research. NPJ Biomedical Innovations, 2(1), 14. https://doi-org.bunnlibrary.idm.oclc.org/10.1038/s44385-025-00019-9