UCLA Team Builds Programmable RNA Organelles Inside Living Cells

by Clarence Oxford
Los Angeles, CA (SPX) Apr 29, 2026
Researchers at UCLA have developed a method to construct programmable artificial organelles inside living cells using RNA as both the structural material and the assembly blueprint, an advance they say opens new possibilities in nanomedicine and cell engineering.

The work, published April 29 in Nature Nanotechnology, centers on membrane-less organelles known as biomolecular condensates - droplet-like clusters of proteins and RNA that cells use as temporary workspaces for concentrated molecular activity. The UCLA team's approach encodes assembly instructions directly into RNA sequences and structures, rather than relying on naturally aggregating proteins as previous methods have done.

To drive condensate formation, the researchers designed short RNA strands that fold into structures they call nanostars, each with three or more arms. At the tips of these arms are complementary sequences known as kissing loops, which bind to each other and allow the nanostars to self-assemble into larger networks. Because RNA follows predictable base-pairing rules, these structures can be programmed to form in controlled and specific ways.

The team demonstrated the ability to tune the size, internal composition, and intracellular location of the resulting condensates. By modifying the number and length of nanostar arms, or the binding strength of their interactions, researchers could direct where condensates form within the cell - including shifting them between the cytoplasm and the nucleus - each compartment associated with distinct biological functions.

"This research is a step toward architectural engineering of the cell interior," said study lead Elisa Franco, a professor of mechanical and aerospace engineering and bioengineering at the UCLA Samueli School of Engineering. "By using RNA as a building material, we can create customizable compartments inside cells while using fewer cellular resources than protein-based approaches."

Study first author Shiyi Li, a bioengineering doctoral candidate in Franco's Dynamic Nucleic Acid Systems Lab, described the condensates as functioning like newly created, temporary rooms inside the cell. "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," Li said.

The distinction from prior work lies in where the assembly logic resides. Earlier synthetic biology approaches to artificial condensates depended on the intrinsic aggregation behavior of certain proteins. The UCLA method shifts that logic entirely into the RNA sequence itself, allowing designers to specify interaction rules computationally before synthesis.

As the technology matures, researchers say the programmable condensates could underpin synthetic organelles with specialized biological functions - acting as confined reaction chambers inside living cells for gene regulation, targeted drug delivery, or other applications in cell engineering.

Other authors on the paper include Neil Lin, associate professor of mechanical and aerospace engineering and bioengineering at UCLA Samueli; Kathrin Plath, professor at the UCLA Broad Stem Cell Research Center; Melody Li and Douglas Black, both from UCLA's Microbiology, Immunology and Molecular Genetics Department; project scientist Dino Osmanovic; postdoctoral researchers Anli Tang and Wen Xiao; graduate students Eric Payson, Alexandra Bermudez and Maria Nieto; and undergraduate students Yuna Kim, Kevin Wang, Madison Yang and Diego Dilao.

Research Report: Programmable artificial RNA condensates in mammalian cells