The breakthrough success of mRNA vaccines during the COVID-19 pandemic catapulted RNA-based therapeutics into the spotlight. Today, RNA technologies are looking beyond infectious disease and reshaping the treatment landscape for cancer, rare diseases, autoimmune conditions, and more. Platforms based on mRNA, self-amplifying RNA (saRNA), circular RNA (circRNA), and RNA editing are enabling the precise, programmable expression or suppression of proteins within the body — offering a flexible and scalable alternative to traditional biologics and gene therapies.
Unlike DNA-based therapies, RNA modalities do not integrate into the genome, reducing long-term safety risks while allowing for transient, tunable protein production. Moreover, advancements in lipid nanoparticle (LNP) and viral delivery systems are helping RNA therapies reach target tissues more effectively. As this technology matures, a new generation of startups is moving beyond vaccines to explore RNA’s full therapeutic potential.
Here, we highlight five young biotech companies leading innovation in RNA platforms and applications: Orbital Therapeutics, Shape Therapeutics, Chimeron Bio, Korro Bio, and Replicate Bioscience.
Orbital Therapeutics: Building a Broad RNA Medicines Platform
Orbital Therapeutics, launched in 2022, was purpose-built with a comprehensive platform of established and emerging tools and technologies to develop the next generation of RNA medicines that goes well beyond infectious disease. In 2023, the company completed a $270 million Series A financing led by ARCH Venture Partners — one of the largest initial financings to date for an RNA-focused biotech.
Orbital is pioneering a new class of RNA medicines that overcome historical barriers to protein expression, durability, and delivery — opening the full opportunity of RNA medicines to more tissues and more diseases, and ultimately, more patients. Orbital’s platform integrates proprietary end-to-end innovations in RNA engineering, payload modularity, and targeted delivery, enabling a new class of RNA medicines that have the potential to reprogram the innate immune system.
Backed by an expert team of RNA drug discoverers and developers and company builders, with a vision of bringing programmable RNA medicines to all patients, Orbital is advancing a diverse pipeline across multiple therapeutics areas, initially led by RNA immunotherapies for autoimmune indications. As RNA technologies move beyond single-use vaccines into the realm of chronic and complex disease management, Orbital is positioned to lead the field with a platform designed for breadth, control, and reusability.
Shape Therapeutics: RNA Editing for Precision Medicine
Shape Therapeutics is redefining precision medicine with its RNA editing platform, which enables transient correction of genetic mutations without altering the underlying DNA. The company’s flagship RNAfix platform leverages engineered RNA-guided proteins, delivered via AAV vectors, to make targeted edits at the transcript level. This transient mechanism reduces the risk of off-target genomic effects and may offer greater safety and reversibility compared with DNA-based gene editing tools like CRISPR.
This therapeutic strategy is particularly compelling for monogenic disorders, where even modest, short-term restoration of protein function can have a transformative impact. Shape’s RNAfix technology is being explored across a range of rare genetic diseases and central nervous system conditions, especially where permanent modification of the genome may carry unacceptable long-term risks.
To achieve efficient delivery, Shape has developed a complementary platform for AI-guided AAV capsid design. This innovation allows the company to engineer novel viral vectors with tailored tropism — targeting specific tissues, such as the brain, liver, or muscle, with high precision. These capabilities parallel Orbital Therapeutics’ delivery strategy but are uniquely focused on integrating AI to optimize capsid performance and payload compatibility.
In 2021, Shape entered into a major strategic partnership with Roche to develop RNA-based therapeutics for neurodegenerative diseases, a collaboration that could exceed $3 billion in value. This deal underscores industry confidence in Shape’s approach and highlights the growing interest in reversible, RNA-level editing as an alternative to permanent DNA interventions.
Compared with the transcript-level editing strategy of Korro Bio or the amplification strategies behind Replicate Bioscience’s saRNA, Shape’s RNAfix is designed for precise, one-time correction of disease-causing mutations. By focusing on diseases with high unmet need and tractable delivery targets, Shape Therapeutics is helping to build a new therapeutic category: programmable, tissue-specific, and reversible RNA editing.
Chimeron Bio: Self-Amplifying RNA for Potent Intracellular Delivery
Chimeron Bio is pioneering a new generation of self-amplifying RNA (saRNA) technologies to drive high levels of therapeutic protein expression with fewer doses. Their proprietary ChaESAR (Chimeron enhanced self-amplifying RNA) platform packages saRNA within virus-like particles (VLPs), mimicking the body's natural delivery systems to improve intracellular uptake and enhance stability within target cells.
Originally focused on developing saRNA vaccines, Chimeron has strategically expanded its pipeline to include therapeutic applications in oncology, rare diseases, and chronic inflammatory disorders. The ChaESAR platform is designed to amplify RNA signal once inside the cell, enabling strong and sustained expression of therapeutic proteins from small initial doses. This can be particularly advantageous for diseases where high-dose delivery is challenging or frequent re-administration is burdensome.
A key differentiator for Chimeron is its focus on non-replicating viral-like particle delivery—providing a potential alternative to LNP systems used by many other saRNA developers, including Replicate Bioscience. This design may reduce innate immune activation and improve delivery specificity, especially in immunologically sensitive or hard-to-penetrate tissues.
Chimeron’s platform also occupies an intriguing middle ground between Orbital Therapeutics’ broad RNA toolkit and Replicate’s immuno-oncology–focused self-replicating RNA (srRNA) approach. Like Replicate, Chimeron is pursuing immune modulation and protein replacement, but its emphasis on VLPs could offer distinct advantages in targeting and endosomal escape. Its transient yet potent expression strategy also contrasts with Korro Bio’s precision RNA editing, offering an alternative mechanism for therapeutic modulation.
As the company moves its therapeutic programs forward, it is building out manufacturing and formulation capabilities to support clinical translation. With the growing recognition of saRNA as a powerful class of therapeutic RNA, Chimeron Bio is positioning itself as a differentiated player focused on intracellular efficiency, durability, and delivery innovation.
Korro Bio: Advancing RNA Editing for Precision Therapeutics
Korro Bio is advancing a novel class of RNA editing therapies that harness the body’s existing cellular machinery to make precise, reversible edits at the RNA level. Rather than permanently altering the DNA, Korro’s platform targets adenosine-to-inosine (A-to-I) base editing on mRNA transcripts — a naturally occurring process that the company has engineered for therapeutic applications. This approach enables the modulation of protein function in a transient and potentially safer way than DNA-based genome editing.
Korro’s lead programs focus on genetically defined diseases where a single RNA base change can restore functional protein. One of its early targets is alpha-1 antitrypsin deficiency (AATD), a rare liver and lung disorder caused by a misfolded protein. By precisely correcting the RNA transcript, Korro aims to increase the expression of functional alpha-1 antitrypsin without permanently modifying the patient’s genome. This strategy is particularly compelling for liver diseases, where RNA turnover is high and redosing is feasible.
The company’s proprietary OPERA™ platform — Optimized Platform for RNA Editing by Recruitment of ADAR — is designed for high specificity and minimal off-target activity. It leverages endogenous ADAR enzymes to convert targeted adenosines into inosines, which are interpreted as guanosines by the cell’s translational machinery. This allows for protein recoding at the RNA level with temporal control and the potential for reversibility.
In contrast to Shape Therapeutics, which also operates in the RNA editing space using engineered proteins and AAV delivery, Korro focuses on leveraging native ADAR activity and non-viral delivery systems. This positions the company as a differentiated player with potentially fewer immunogenicity risks and broader applicability across tissues.
Following Wave Life Sciences’ clinical success in RNA editing for AATD, investor confidence in the field surged, and Korro Bio is now advancing its own candidates toward the clinic. With backing from top-tier biotech investors and a leadership team with deep RNA experience, Korro is poised to be a frontrunner in the development of safe, transient, and precise RNA editing therapeutics.
Replicate Bioscience: saRNA Immunotherapies to Reprogram the Immune System
Replicate Bioscience is pioneering the use of srRNA for immunotherapies aimed at reprogramming the immune system to fight cancer and persistent viral infections. Built on a foundation of synthetic biology and advanced RNA engineering, Replicate’s platform enables sustained protein expression from low-dose administration, enhancing the potency of immunological responses while minimizing the need for repeated injections.
The company’s srRNA technology differs from conventional mRNA by incorporating replicase machinery that drives amplification of the RNA payload within cells. This allows for robust intracellular production of therapeutic proteins, cytokines, or antigens over extended periods, offering potential advantages in immuno-oncology and chronic infection contexts. In oncology, this could translate to stronger tumor targeting with fewer doses; in infectious disease, it supports both therapeutic and prophylactic strategies against pathogens such as cytomegalovirus, Epstein-Barr virus, and others.
Replicate’s lead programs include vaccines and immunotherapies targeting solid tumors and herpesvirus family members, with promising preclinical data suggesting the potential to reshape immune dynamics in difficult-to-treat conditions. The company is also pursuing a collaborative project with the U.S. Department of Defense to explore srRNA as a rapid-response platform for biodefense and emerging infectious threats — underscoring the flexibility of its technology in time-sensitive or resource-limited scenarios.
Unlike Chimeron Bio, which uses virus-like particles to deliver saRNA constructs, Replicate relies on LNP-based delivery with optimized formulation to support repeatable and systemic dosing. While Orbital Therapeutics and Korro Bio are building platforms for redosable protein expression and precision RNA editing respectively, Replicate’s focus is on dynamic immune activation — mobilizing T cells, NK cells, or antibody-producing B cells in real time.
With an experienced leadership team and growing investor support, Replicate is advancing the clinical translation of srRNA as a novel modality that complements — and potentially surpasses — conventional mRNA therapies in certain immunological contexts. As the field of RNA therapeutics matures, Replicate Bioscience stands out for its targeted, immunologically driven use of RNA amplification to achieve disease modification and durable responses.