Seoul biotech’s redesigned method makes circular RNA up to seven times more efficient to build, widening what RNA medicine can treat.
There’s a version of RNA that doesn’t behave like the RNA most people have heard of. Instead of a straight strand, it loops into a closed circle, no loose ends for the body’s enzymes to grab onto and chew apart. That stability is the whole appeal. It’s also, for years, been the hard part to manufacture, especially once you’re working with a long stretch of genetic code.
South Korean biopharmaceutical company Rznomics says it has cracked a meaningful piece of that problem. In a study published 4 September in Nucleic Acids Research, the company’s researchers describe an upgraded version of their circular RNA (circRNA) production platform, one that produces the closed-loop molecules far more reliably than before, even at sizes previously considered impractical [1].
Why should a longevity-focused reader care about a manufacturing tweak? Because durability is currency in RNA medicine. Circular RNA holds up longer inside the body than the linear kind, which means fewer doses, steadier protein output, and a sturdier backbone for the vaccines and protein therapeutics that next-generation longevity and regenerative medicine will likely depend on. A production bottleneck upstream is a bottleneck for all of that downstream.
Finding the right spot to fold
Rznomics’ underlying technology, called Self-Targeting and Splicing (STS), lets an RNA molecule fold itself into a circle during transcription, essentially self-assembling rather than needing to be stitched closed afterward. The trouble is that circularization efficiency tends to drop as the RNA gets longer, which limits the size of genes a company can practically produce this way.
The team went looking for why. It turns out the location of the targeted folding site within the RNA sequence matters enormously, something the researchers hadn’t fully appreciated before running a systematic screen. Pick the wrong spot and the molecule struggles to close. Pick the right one, and it doesn’t.
From there, the engineering got more specific. Researchers modified a structural piece of the system called the P1 construct, adding a short polyA10 sequence along with an antisense sequence designed to grip the target site more tightly. Combined with smarter site selection, the tweak improved self-circularization efficiency by roughly sevenfold over the original STS design.
The real test came with a large RNA: a sequence encoding Factor VIII, the blood-clotting protein, running about 7.8 kilonucleotides long, sizable by circRNA standards. The optimized method produced roughly twice the circularization efficiency of the Permuted Intron-Exon (PIE) approach, which had been the field’s go-to technique for this kind of work.
What it opens up
That result matters because it pushes circRNA production into territory that used to be mostly out of reach: genes approaching 8 kilo-nucleotides, large enough to cover a meaningful slice of therapeutically relevant proteins rather than just small fragments.
“By establishing a foundation for the efficient and robust production of circRNA even from large RNA molecules, we expect this technology to help broaden the potential horizons of circRNA application,” said Dr Kyung Hyun Lee, the study’s first and co-corresponding author.
Rznomics CEO Dr Seong-Wook Lee framed it as a platform move rather than a single result.
“This milestone further advances our proprietary circRNA platform and strengthens its potential for practical applications,” he said. “Moving forward, we plan to expand its utility across diverse therapeutic areas, including CAR-T therapies.”
That last mention is worth sitting with. CAR-T, the cell therapy approach already reshaping cancer treatment, is exactly the kind of complex, precision-engineered medicine that benefits from RNA components that don’t degrade the moment they hit the bloodstream. If circRNA can be manufactured reliably at the sizes CAR-T and other advanced therapies require, it becomes a plausible building block for treatments aimed at the diseases of aging, not just oncology.
Rznomics is a clinical-stage company built around trans-splicing ribozyme technology for RNA editing. Its lead oncology candidate, Taspitimagene advec (RZ-001), holds a Regenerative Medicine Advanced Therapy designation from the FDA. The company signed a research collaboration with Eli Lilly in May 2025 and was listed on South Korea’s KOSDAQ exchange that December.
None of this means a circRNA vaccine or therapy is imminent. What it does mean is that one of the manufacturing walls standing between circRNA’s theoretical promise and its practical use just got a little lower, and the field’s toolkit for building durable, longevity-relevant medicines got a little bigger.
