Orna Therapeutics is a biotechnology company advancing a new generation of genetic medicines. Building on the public awareness of RNA-based treatments, the company is focused on developing therapies that address the limitations of previous technologies. Its work aims to engineer new treatments for a range of human diseases, placing it among innovators defining the next chapter of therapeutic development.
The Science of Circular RNA
At the heart of Orna’s approach is a molecule known as circular RNA, which the company has engineered and named oRNA. Unlike the linear messenger RNA (mRNA) used in certain vaccines, which can be pictured as a string with a distinct beginning and end, oRNA is a closed loop, similar to a necklace. The company developed a process where a specially designed linear RNA molecule folds back on itself and joins its ends together, forming a continuous, circular strand.
This circular architecture provides a natural defense against enzymes in the body called exonucleases. These enzymes break down linear RNA by attacking its exposed ends. Since oRNA has no ends, it is inherently more resistant to this type of enzymatic degradation.
To make these circular molecules therapeutically active, they must instruct the cell’s machinery to produce a desired protein. Orna has incorporated genetic elements known as internal ribosome entry sites (IRES) into its oRNA constructs. These IRES sequences act as signals, directing the cell’s ribosomes to begin the protein-building process without needing a conventional starting cap. The company has developed a library of these IRES elements, allowing for the fine-tuning of protein expression.
Advantages of the oRNA Platform
The structure of oRNA gives rise to several benefits for therapeutic development. Its resistance to degradation means that a single oRNA molecule can persist inside a cell for a longer period than a linear mRNA molecule. This extended half-life allows for more sustained and durable production of a therapeutic protein from one dose.
This increased stability and longevity directly impact the potential potency of a therapy. Because each oRNA molecule can be read by the protein-making machinery multiple times before it is cleared, it can generate a larger quantity of the necessary protein. This efficiency could translate to lower required doses, as demonstrated in preclinical animal models.
The production process for oRNA is also simplified compared to linear mRNA. It does not require the addition of special “cap” and “tail” structures that linear mRNA needs for stability and function. This streamlined manufacturing can lead to a more uniform product, which simplifies packaging the oRNA into the lipid nanoparticles (LNPs) used for delivery.
Therapeutic Applications and Pipeline
Orna is leveraging its oRNA platform to develop treatments for several serious diseases, with a primary focus on oncology and genetic disorders. A leading area of development is its in vivo CAR-T therapy, an approach to fighting cancer. This method involves administering oRNA packaged in LNPs directly to the patient, where it enters their immune cells and instructs them to become cancer-fighting CAR-T cells inside the body.
This in vivo strategy differs from conventional CAR-T therapies, which require extracting a patient’s immune cells, engineering them in a lab, and then re-infusing them. Orna’s lead program, ORN-101, is designed to bypass this complex external process. The goal is to create an “off-the-shelf” treatment that could be administered more easily, potentially without the harsh chemotherapy regimen, known as lymphodepletion, that patients undergo with traditional CAR-T.
Beyond cancer, the company is applying its technology to genetic disorders where the body fails to produce a functional protein. The durability of oRNA makes it a suitable candidate for these conditions, as it can provide sustained production of the missing protein. To deliver these therapies, Orna is developing specialized LNP delivery systems, including its panCAR™ platform to target immune cells and its STEM™ platform to reach stem cells in the bone marrow.
Key Partnerships and Collaborations
The potential of Orna’s oRNA technology has attracted investment from pharmaceutical leaders, resulting in a major collaboration with Merck. This partnership was established to discover, develop, and commercialize new vaccines and therapeutics. The collaboration focuses on infectious diseases and oncology.
Under the terms of the agreement, Orna received an upfront payment of $150 million from Merck. The collaboration also includes the potential for an additional $3.5 billion in payments based on specific development, regulatory, and sales milestones. Merck also made a $100 million equity investment in Orna.
This partnership provides Orna with substantial resources and leverages Merck’s experience in clinical development and manufacturing. While collaborating with Merck on specific programs, Orna retains full rights to its oRNA-LNP platform technology. This allows it to continue advancing its own wholly owned programs in areas like oncology and genetic disease.