Circular RNA Emerges as Next-Generation Therapeutic Platform with Big Pharma Backing
核心洞察
Circular RNA (搜索) (circRNA) offers up to 75-fold increased RNA half-life and 50-fold enhanced protein expression compared to conventional mRNA, enabling lower-dose, less toxic gene therapies.
Circio (搜索)'s circVec platform demonstrated 40-fold boosted AAV (搜索) activity in the heart in vivo, attracting a fully funded collaboration with a top-5 pharma company and a $65 million fundraising in 2026.
Major acquisitions underscore industry confidence: BMS acquired Orbital for $1.5 billion and Lilly acquired Orna for its circular RNA (搜索) platform, both at preclinical stages.
Circular RNA (搜索) (circRNA) is rapidly transitioning from a biological curiosity into one of the most closely watched therapeutic platforms in the pharmaceutical industry. Once dismissed as an experimental artifact, circRNA is now attracting multibillion-dollar acquisitions, major pharma collaborations, and substantial investor capital—driven by its ability to deliver longer-lasting protein expression, enhanced stability, and potentially safer, more cost-effective genetic medicines.
Erik Digman Wiklund, CEO of Circio (搜索) and co-discoverer of human circular RNA (搜索), has been at the center of this transformation. "The natural biology of circular RNA has always been compelling from a therapeutic standpoint. What has changed is our ability to harness the advantages of cRNA," Wiklund told BioSpectrum Asia during the BIO International Convention 2026.
The Stability Advantage
The fundamental appeal of circRNA lies in its structure. Unlike linear mRNA, circular RNA (搜索) lacks free ends, making it far less sensitive to enzymatic degradation. This translates directly into extended half-life and sustained protein expression. Circio (搜索)'s circVec platform has demonstrated up to 75-fold increased RNA half-life and up to 50-fold enhanced protein expression compared to conventional mRNA-based vector systems.
"This can be applied to areas such as AAV (搜索) gene therapy to considerably increase expression of the transgene, as well as expanding the therapeutic window by letting you achieve the same therapeutic effect at a lower vector dose," Wiklund explained. "Put simply, better efficacy and less toxicity, delivered at lower therapeutic doses and reduced cost."
Addressing Gene Therapy's Core Challenges
Toxicity in AAV (搜索) gene therapy is largely a dose-dependent problem, and circRNA offers a direct solution. Circio (搜索) has demonstrated that circRNA-based gene expression can boost AAV activity by 40-fold in the heart in vivo, suggesting that the circVec system can deliver equivalent therapeutic effects at substantially reduced doses.
"Vector dose is one of the primary drivers of manufacturing cost in AAV (搜索) gene therapy. Lower dose requirements mean lower cost per patient, which is the lever the field needs to make these treatments more accessible," Wiklund noted. "cRNA doesn't solve every manufacturing challenge, but it addresses one of the most fundamental constraints."
From Academic Discovery to Therapeutic Platform
The journey of circular RNA (搜索) from laboratory oddity to therapeutic contender began with foundational discoveries published in the early 2010s. Wiklund and Thomas Birkballe Hansen, now Circio (搜索)'s Chief Technology Officer, published the first functional characterization of circular RNA in human cells in 2011. The field gained critical momentum in 2013 when Hansen published a landmark paper in Nature demonstrating biological functionality and numerous circular RNA copies.
"Thomas published a paper in Nature showing biological functionality and numerous circular RNA (搜索) copies, and I think that parked all the doubt that this was just some artifact or biologically irrelevant," Wiklund recalled. That paper has since accumulated more than 7,000 citations.
The biological mechanism that Hansen elucidated—circRNA functioning as a microRNA (搜索) sponge—revealed how these molecules regulate gene expression. Circular RNA (搜索) contains numerous binding sites for microRNAs, sequestering them until the circle is cleaved, at which point the microRNAs are released simultaneously to trigger rapid downstream effects. These circRNAs are highly present in the eye and central nervous system, tissues requiring fast responses to external stimuli.
Big Pharma Validation
The pharmaceutical industry's conviction in circRNA's potential is reflected in recent dealmaking. Bristol Myers Squibb (搜索) acquired Orbital Therapeutics (搜索) in November 2025 for $1.5 billion, and Eli Lilly acquired Orna Therapeutics (搜索) earlier in 2026 for its circular RNA (搜索) platform. Both companies were preclinical-stage at the time of acquisition.
"For comparison, I worked at a company called Algeta, which Bayer acquired in 2014 for around $3 billion—but that was after approval. The drug was already on the market. Now you are seeing companies acquired for two-thirds of that value before they have even entered the clinic," Wiklund observed. "For me, that says a lot about where the field believes circular RNA (搜索) is heading."
Circio (搜索) itself attracted significant investor attention following data presented at ASGCT in 2025, where circVec showed superior in vivo transgene expression in muscle, heart, and spleen compared with linear mRNA. A top-5 pharmaceutical company subsequently initiated a fully funded gene therapy collaboration with Circio, effectively validating the platform. These developments underpinned Circio's successful $65 million fundraising in 2026.
A Differentiated Approach
While companies such as Orna, Orbital, and Flagship-founded Laronde (搜索) focus on synthetic, in vitro-transcribed circular RNA (搜索)—essentially a circular version of the Moderna mRNA approach—Circio (搜索) has pursued a distinct strategy. The company's platform creates viral and synthetic DNA vectors capable of expressing genetic payloads as circular RNA rather than linear RNA, aiming to boost the potency of vector-based therapeutics.
"We believed the advantages of circular RNA (搜索) should also apply in any setting where a gene is expressed from a vector," Wiklund said. "It was a niche within circular RNA that, as far as we could see, almost no one else was pursuing."
Therapeutic Frontiers
Cardiology represents Circio (搜索)'s most mature data area. Genetic and chronic heart diseases constitute a major unmet medical need, and the heart has historically been a challenging target for AAV (搜索) gene therapy. The Circio/AaviGen collaboration, announced in May 2026, combines circVec with engineered, heart-targeted capsids specifically aimed at making low-dose, high-precision cardiac gene therapy a clinical reality.
Ophthalmology and CNS disorders are additional areas of active investigation. "Durable, low-immunogenicity RNA expression in the eye and brain is a difficult challenge, and circRNA's properties address some of the core barriers," Wiklund explained.
Looking further ahead, in vivo cell programming represents a major opportunity. "The idea that one could reprogram a patient's immune cells in their body, rather than through an expensive and logistically complex ex vivo process, would fundamentally change access to cell therapy," Wiklund said.
Beyond protein and CAR expression, the stability properties of circRNA make it a powerful platform for non-coding applications, including miRNA sequestration, RNA-protein interactions, circular guide RNAs for gene editing, and even PROTAC scaffolds for targeted protein degradation.
"I think everyone will eventually switch to circular RNA (搜索) for applications where RNA is being used to express a therapeutic protein or antigen," Wiklund predicted. "In the majority of therapeutic applications it is simply going to be so much better that people will have to make that transition."