RNA can instruct your body to make customized, highly efficacious medicines, with few side effects and at low cost.
Synthetic Genomics has engineered a proprietary RNA replicon platform to selectively stimulate the immune system and deliver targeted therapies produced within a person’s own body. Our RNA platform overcomes common shortcomings of traditional replicon and messenger RNA (mRNA) technologies, enabling a new class of vaccines and combination therapies to combat cancer and infectious diseases.
RNA replicons use the body’s cellular machinery to produce ample amounts of proteins that can trigger a protective immune response (to prevent the flu, for example) or produce a therapeutic response to treat diseases like cancer. Our RNA replicons are powered by an “engine” that carries specific instructions to cells to replicate RNA. The body’s natural machinery takes over from there, quickly converting the genetic instructions into thousands of copies of RNA. The RNA replicon is translated to produce the desired antigens or other proteins that trigger the body’s immune response or deliver a direct therapeutic effect.
Conventional development and manufacturing of protein-based medicines requires costly and complex manufacturing processes. Our RNA replicon is a synthetic platform that has the potential to undercut expensive vaccine and therapeutic production costs — eliminating the need for large manufacturing facilities. In addition, the technology is tunable, or adjustable, so it can be quickly adapted to respond to mutations in disease-causing pathogens or to incorporate new therapeutic molecules.
How Our RNA Replicon Is Different
Bypass inflammation-mediated shutdown
Inflammation-mediated shutdown suppresses vaccine or therapeutic efficacy and can be observed with traditional mRNA-based approaches. Cells stop producing proteins in response to either sterile inflammation, which can be triggered by chemotherapy, radiation, immune-therapies, high-fat diets, obesity or imbalanced microbiota, or infectious inflammation, which is often seen in people with viral, bacterial or parasitic co-infections. Thus, inflammation is an underlying condition in many patient populations, which can curtail the utility of other RNA-based therapeutic platforms. Our proprietary RNA replicon is designed to specifically bypass this mechanism — but without preventing cells from promoting inflammation, which is important for driving immune response.
Superior in vivo protein expression
mRNA has a rapid peak (roughly 24 hours) and decay (signal lost in 5-7 days). By contrast, our RNA replicon platform is capable of durable expression beyond 28 days for therapeutic proteins. Once administered into a cell host, our engineered RNA replicon generates tens of thousands of copies that direct the production of protein within hours.
Multigenic and tunable
Traditional vaccines are limited to expressing a single antigen to trigger immune response. When multiple proteins are included, this has traditionally required separate manufacturing processes for each protein. Our RNA replicons can express multiple antigens simultaneously, with the potential to trigger a broader, more effective immune response. Furthermore, each gene is individually controllable, allowing customization for individual pathogens, diseases, or therapeutic protein production. This is important for balancing ratios of heavy and light chains for antibody expression, or for avoiding toxicity when co-encoding immunostimulatory molecules in vaccines.
Superior immune responses
Conventional or modified mRNAs are poor inducers of T cell responses. Our engineered RNA replicon platform, however, increases the magnitude and quality of acute and memory T cell responses. It produces strong, protective antibody responses and holistically engages the immune system, which is critical in complex infectious disease and cancers.
Cost-effective, scalable, and rapid manufacturing
Affordable and rapid manufacturing enables a fast response to emerging disease threats. With RNA replicons, a single-liter bioreactor can produce more than five million doses, allowing for a tiny GMP manufacturing footprint when compared with traditional technologies. The self-amplifying nature of our RNA replicon platform results in a high-potency product (projected human vaccine doses of one microgram or less) that can be produced at pennies per dose and has an increased safety profile. Importantly, the fully synthetic manufacturing allows for vaccine production within weeks instead of months. Our approach is highly scalable, allowing production, purification, and formulation on a personalized scale (milligram quantities) or at scales compatible with global distribution (gram quantities).
BioXpTM 3200 System for Precision Medicine
We can rapidly manufacture DNA constructs on demand and are working toward automating the production of DNA- and RNA-based precision medicines.
Synthetic Genomics has developed an automated manufacturing process that significantly reduces the time it takes to create DNA constructs for therapeutic research and development programs, clearing the path to precision medicines. Laboratory workflows that once took several months can be done in a matter of few weeks, if not days.
At the core of this process is the BioXp 3200 System, the world’s first DNA printer, an automated instrument that enables any biotechnology, pharmaceutical, academic, or government laboratory to start with electronically transmitted sequence data and create DNA including genes, plasmids, and genetic elements.
More information about the BioXp, including the system’s benefits, and instrument applications that support a complete biotherapeutic research and development workflow is available at SGI-DNA, our subsidiary for commercial products and services.
Personalized medicine represents an outstanding opportunity to combine the flexibility of the BioXp and the RNA replicon technology. Speed is paramount in a personalized medicine setting where time is of the essence. The potential to develop multiple, personalized, RNA replicon cancer vaccine DNA constructs in parallel on a single BioXp system could be truly transformational in the personalized medicine field.
In 2013, shortly after Synthetic Genomics built the BioXp prototype, an international health organization contacted the company with a global health problem that needed solving. Two men had recently died in China after contracting the H7N9 bird flu, and fears of a global pandemic were growing. Although methods existed to produce a bird flu vaccine, it wouldn’t be available for at least six months. The only option for vaccine production was a slow manufacturing process developed 70 years ago; the virus would need to be taken from infected patients, packaged, and mailed to a facility where scientists would inject the virus into chicken eggs. Those eggs would then incubate for several weeks to prepare the virus for the start of a multi-step, multi-month vaccine manufacturing process.
The BioXp enabled a better option. Synthetic Genomics’ scientists downloaded the virus’ DNA sequence as soon as it became available, and within 12 hours the BioXp had synthesized the DNA. Novartis quickly started turning that DNA into a flu vaccine. For the first time, a flu vaccine was produced ahead of time for a new and potentially dangerous strain of the flu.
In the not-too-distant future, we anticipate this type of approach will have applications beyond producing speedy flu vaccines. It also can help patients battling cancer or other complex diseases that require a treatment tailored to specific mutations of the virus or infection.