For decades, synthetic biologists have dreamed of creating life from scratch—assembling living cells from non-living components. One major obstacle? Proteins. These molecular machines drive nearly every biological process, yet their synthesis requires an intricate, multi-step process involving over 150 genes. Now, a research team at Heidelberg University has sidestepped this challenge using RNA origami, a breakthrough that could reshape the future of synthetic cells.

Led by Prof. Dr. Kerstin Göpfrich at the Center for Molecular Biology, the team has successfully engineered RNA-based nanotubes that self-assemble into cytoskeleton-like structures—providing stability, shape, and mobility to artificial cells. Their findings, published in Nature Nanotechnology, offer a glimpse into a future where synthetic cells build themselves without the need for protein synthesis.

Rethinking the Central Dogma

In natural cells, proteins are synthesized through the central dogma of molecular biology: DNA is transcribed into RNA, which is then translated into proteins that fold into functional shapes. This complexity has long posed a challenge for synthetic biology, requiring a minimal gene set just to replicate this process. But Göpfrich and her team are taking a different approach: what if synthetic cells could bypass protein synthesis entirely?

Enter RNA origami. Instead of relying on proteins, this technique uses the inherent multifunctionality of RNA to build structural components. It starts with a computer-designed DNA sequence that encodes the desired RNA shape. Once synthesized, RNA polymerase reads the DNA blueprint and transcribes it into self-folding RNA structures. Advanced algorithms ensure precise folding, making it possible to design intricate architectures at the nanoscale.

Building the RNA Cytoskeleton

Using this method, the researchers crafted RNA nanotubes just a few microns long—resembling the cytoskeleton that gives cells their structure. To test their functionality, the team embedded these RNA-based frameworks inside lipid vesicles, a common model for synthetic cells. By incorporating RNA aptamers, they anchored the artificial cytoskeleton to the cell membranes, demonstrating control over cell-like architecture without relying on protein-based scaffolds. Genetic tweaks to the DNA template further refined the mechanical properties of these RNA structures.

Compared to DNA origami, RNA origami offers a unique advantage: synthetic cells could potentially produce their own building blocks autonomously. “This could open new perspectives on the directed evolution of such cells,” Göpfrich explains. The ultimate goal? Engineering fully RNA-based molecular machinery capable of sustaining synthetic life.

Toward an RNA-Driven Future

This breakthrough moves synthetic biology closer to constructing autonomous, life-like systems. If RNA can replace proteins for essential cellular functions, scientists could create entirely new life forms, redefine biotechnology, and even explore origins-of-life questions.

The project received funding from an ERC Starting Grant, the Human Frontier Science Program, Germany’s Federal Ministry of Education and Research, the Baden-Württemberg Ministry of Science, and the Alfried Krupp Prize. As RNA technology continues advancing, synthetic cells without proteins may soon shift from an experimental marvel to a foundational tool in bioengineering.