Touchlight's enzymatically manufactured dbDNA™ (doggybone DNA) is a transformative innovation in the industrialization of DNA production, eclipsing traditional plasmid DNA (pDNA) with a suite of enhancements that redefine biomanufacturing for a wide range of genetic medicines. dbDNA sets a new standard in speed, purity and scalability, advancing the potential of advanced therapies, including viral vectors, gene-edited cell therapies, and DNA vaccines. Within the competitive landscape of synthetic DNA companies, Touchlight stands out owing to dbDNA’s robustness, scalability, ability to amplify complex sequences, and — importantly — having been clinically adopted across multiple modalities in the United States and Europe. This article delves into the company’s journey from its visionary foundation to becoming an industry pioneer, showcasing its robust IP portfolio, regulatory triumphs, and unwavering commitment to innovation in enzymatic DNA technology, ensuring a leading position in the rapidly evolving realm of genetic medicine. With a range of contract development and manufacturing services, expanded production capacity, and continuous innovation, Touchlight continues to drive the adoption of synthetic DNA to realize its potential to enable the genetic medicine revolution.
The Touchlight Story
Touchlight was founded in 2007 by visionary Executive Chairman Jonny Ohlson with a mission to revolutionize DNA-based medicine. Understanding the potential unlocked by advances in genome sequencing, Ohlson steered the company to tackle the pressing need for enhanced methods of DNA production, seeking to transcend the speed, safety, cost, and capacity constraints inherent in traditional pDNA production via bacterial fermentation.
Embarking on this challenge, Touchlight's research culminated in the creation of the enzymatically amplified dbDNA — a groundbreaking alternative to pDNA. By 2015, Touchlight’s core patent families were granted, and the company focused on the industrialization of the platform. Successful feasibility studies focused on viral vectors, followed by gene editing. In 2018, Touchlight marked a significant leap in scalability with its first gram-scale manufacturing runs, leading to the commencement of cGMP operations in 2019. A transformative $125 million investment in 2021 propelled the expansion of its Hampton, UK–based facility, now boasting 11 state-of-the-art GMP production suites. Privately held and underpinned by an entrepreneurial ethos, Touchlight has emerged as a dynamic force enabling the future of genetic medicines. The company offers versatile contract development and manufacturing services, producing dbDNA, which is indispensable both as a critical starting material and as an active pharmaceutical ingredient in a multitude of advanced therapies — ranging from DNA and mRNA vaccines to cell and gene therapies — among other products, such as Z-dbDNA and MegaBulb DNA (mbDNA).
With a portfolio of more than 170 clients as of early 2024, Touchlight's collaborative and innovative spirit is evident in its sustained R&D efforts, which not only aim to meet the current demand but to push the boundaries of DNA technology by providing the toolbox for the next generation of therapeutic breakthroughs.
dbDNA Basics
dbDNA is a double-stranded, linear, covalently closed DNA construct produced via rolling circle amplification from a circular template.1 It contains no bacterial sequences or antibiotic-resistance genes, which presents a significant advantage, as regulators increasingly seek to limit their use to avoid wider dissemination of genes that promote bacterial resistance to key antibiotic drugs.2 An amplification enzyme and a processing enzyme are used to quickly produce high-quality product. Because dbDNA can incorporate genes of interest of up to 30 kilobases in size and with much higher complexity than can be produced using conventional bacterial fermentation, the potential therapeutic applications are numerous and include transient transfection production of the most widely used vectors in cell and gene therapy, such as lentiviral and adeno-associated viral (AAV) vectors. 
During dbDNA amplification, a template of circular DNA and ɸ29 DNA polymerase are employed to generate long double-stranded concatemers of DNA. Protelomerase is then used to cleave at specific recognition sites and covalently close the linear DNA, creating many copies of dbDNA, while restriction enzymes and exonucleases degrade the backbone sequences. The DNA is purified via chromatography and subjected to filtration and filling.
One of dbDNA's most remarkable features is its small manufacturing footprint. Processes that run at less than 5-L scales can produce equivalent yields to what can require fermentation batches of well in excess of 50 L, and even up to 300 L, and our R&D team has demonstrated the capability to further improve yields by several fold. Enzymatic amplification of DNA using the platform has demonstrable linear scalability, which is less assured with conventional methods. The enzymatic production process not only avoids potential impurity and contamination concerns that result from fermentation, like unwanted bacterial DNA sequences, endotoxin, and large quantities of biological waste, but also maintains high fidelity, even for very complex sequences.
Touchlight provides dbDNA in various grades — off-the- shelf Catalogue, Discovery, Research, Smart-GMP, and GMP — supporting a range of needs from small-scale experimental projects to early-phase development, all the way to clinical and commercial manufacturing. In 2022, the U.S. Food and Drug Administration (FDA) accepted its Drug Master File (DMF) — making Touchlight the first company offering a synthetic DNA product to achieve this crucial milestone, cementing its leadership position in the synthetic DNA space.
Overcoming the Limitations of pDNA
The ongoing surge in genetic medicine has highlighted critical shortcomings in pDNA production, which are especially magnified under the pressure of high-demand scenarios. This was most evident during the exploding demand for rapid development and production of mRNA vaccines during the COVID-19 pandemic, but demand is likely to continue to grow as more advanced therapies are approved, especially therapies targeting prevalent rather than rare diseases. The bacterial fermentation process, standard in pDNA synthesis, is hampered by slow production and risks of carrying through bacterial cell components, including bacterial genomic DNA and endotoxins. pDNA itself typically contains antibiotic-resistance genes and bacterial sequences that enable production through recombinant methods in Escherichia coli. Furthermore, scalability of pDNA manufacturing is constrained by the yield and purity challenges inherent in the fermentation process — the real challenge is not adding capacity but minimizing cost of goods sold (COGS) while maintaining the necessary quality standards in these complex processes at scale. Altogether, the limitations of pDNA manufacturing underscore the urgent need for scalable, cleaner and faster DNA production methods.
To resolve some of the known challenges of pDNA, a number of players are bringing innovative products to market. Novel bacterially derived vectors, such as nanoplasmids and minicircles, aim to eliminate bacterial sequences but still suffer from the challenges of fermentation. Novel synthetic products have also begun to emerge. Touchlight’s process is differentiated from other competitor technologies owing to its high degree of optimization for both scalability and production of complex sequences. Touchlight’s process avoids thermal cycling, and patented reagent compositions uniquely enable Touchlight to produce with high yield sequences of high complexity, including those with homopolymers, secondary structures, and repetitive sequences. Touchlight’s process technology also avoids ligation-based methods in downstream purification, which can otherwise require high reaction volumes and have the potential to produce non-target DNA species.
Furthermore, Touchlight's regulatory advancement differentiates the company among synthetic DNA competitors. The company has a DMF accepted by the FDA and open Investigational New Drug Applications (INDs) and Clinical Trial Applications (CTA) for the use of dbDNA in phase I/II clinical trials across modalities in the United States and Europe.
The company's strong intellectual property position, with more than 100 granted patents in key areas of enzymatic DNA production, reflects its innovation and leadership. Touchlight's team of DNA experts boasts an impressive track record in commercialization and experience as a GMP supplier since 2019. Poised to meet future demand, Touchlight's expanded production facility and rapid production process (5-day residence time, including line clearance and cleaning) enables a flexible facility able to serve clients requiring commercial campaigns of hundreds of grams to kilograms per year, alongside fast turnaround of personalized medicines and early clinical demands for smaller quantities.
Enabling Genetic Medicines with dbDNA
The versatile properties of dbDNA render it an exceptional source of DNA for a broad range of pharmaceutical applications. Its ability to enable DNA vaccines, non-viral gene therapies, viral vectors for gene and cell therapies, mRNA therapeutics, and genome-editing technologies has established dbDNA as a pivotal element in the next generation of genetic medicines.
Viral Vectors
Touchlight’s customers are utilizing dbDNA for the production of both adeno-associated viral (AAV) and lentiviral (LV) vectors.3–7 Equivalent or improved titers for several AAV serotypes and LV vectors can be obtained easily using less DNA, even without process optimization, which can yield further significant improvement in titers. The high fidelity of amplification even for complex GOIs, including those containing inverted terminal repeats (ITRs), ensures that unwanted mutations are not introduced. For AAV vectors specifically, the packaging efficiency is increased by an average of twofold or greater, resulting in generation of more doses per batch. Overall, use of dbDNA improves process economics for both LV and AAV vectors, with noticeably reduced costs per dose.
Non-Viral Gene Therapy
dbDNA has shown significant promise as an alternative to pDNA for non-viral gene therapy (e.g., when formulated as lipid nanoparticles (LNPs)). It enables the production of smaller, more uniform LNPs without sacrificing encapsulation efficiency, a notable advantage over pDNA. Furthermore, the structural simplicity of dbDNA allows for the incorporation of larger and more complex genetic sequences, broadening the therapeutic potential of non-viral gene therapy approaches. dbDNA has also shown dose sparing relative to a matched plasmid, offering an improved balance between tolerability and therapeutic effect, a critical parameter in nonviral approaches. Preclinical observations have reported sustained gene expression and a reduction in inflammatory cytokine and liver injury markers, underscoring the clinical relevance of dbDNA in non-viral delivery systems.
Genome Editing
Use of high-purity, low-endotoxin, closed dbDNA instead of pDNA for genome editing has been linked to higher editing efficiency, improved cell viability, and reduced variability across blood donors — expanding its potential in cutting-edge gene-editing applications. Furthermore, the use of dbDNA in genome editing eliminates the need to generate viral vectors for delivery of the genetic material, and its capacity to carry larger gene constructs (> 20kb) expands the potential for developing a broader range of therapeutics.
mRNA Vaccines and Therapeutics
The attributes that make dbDNA advantageous for DNA vaccine and viral vector production translate seamlessly to the manufacture of mRNA vaccines and therapeutics. Short production timelines, scalability, and high-fidelity amplification of complex genetic constructs are key benefits of dbDNA. Touchlight supplies a bespoke product for mRNA, called Z-dbDNA, which is open at the 3' end to enable in vitro transcription (IVT). Z-dbDNA is produced directly from dbDNA, resulting in a high-purity, open-ended IVT template. Z-dbDNA, due to its smaller size compared with a linearized pDNA template, leads to reduced template requirements by mass and can improve IVT yields. These two attributes offer clients benefits in material requirements and improved IVT output.
DNA Vaccines
The COVID-19 pandemic demonstrated the critical advantage of straightforward, rapid, and scalable manufacturing of vaccines, and dbDNA may play a critical enabling role in the development and manufacture of DNA vaccines during the next crisis. In comparative studies, dbDNA-based influenza and SARS-CoV-2 vaccines have demonstrated immune responses in small and large animal models equivalent or superior to those based on pDNA.8–11 With dbDNA, lower doses were required to achieve the same immunogenicity as higher doses of pDNA, indicating its potential for dose-sparing strategies. This efficiency, combined with the ease and speed of scaling up dbDNA production, positions it as a critical asset for vaccine development — particularly in responding to global health challenges.
Additionally, dbDNA vaccines (and DNA platforms in general) produce strong CD8+ T cell responses, critical for controlling tumors in a therapeutic cancer vaccine setting. The speed and flexibility of dbDNA manufacturing further lends itself to an improved offering for neoantigen-based approaches, where time is the critical parameter in the provision of small, individualized patient batches.
Growing Adoption of dbDNA
As a versatile foundation for a new generation of DNA-based products, Touchlight’s dbDNA has become a DNA material of choice for over 170 biotech and top 10 pharma companies as of early 2024. These organizations rely on Touchlight’s contract development and manufacturing services for dbDNA supply for a broad spectrum of applications, including in support of customers developing mRNA, gene editing, and viral vector products (AAV and lentivirus). It is also increasingly being used as an active pharmaceutical ingredient in DNA vaccines and non-viral gene therapy developments. The adoption of dbDNA is demonstrated by the approval of an AAV vector based on dbDNA for first-in-human clinical trials in both the United States and Europe, as well as dbDNA's role in the manufacturing of innovative RNA-based cell-editing therapies, such as VMB-100 (Versameb), currently undergoing clinical evaluation in the United States. With further clinical adoption expected this year in the applications of AAV, non-viral gene therapy, and gene editing, as well as pivotal mRNA trials, Touchlight continues to cement its clinical footprint, delivering on its promise to revolutionize genetic medicine landscape.
Pioneering the Future of DNA Technology
While dbDNA has the potential to have dramatic, positive impacts on the manufacture of genetic medicine from the perspective of improved process economics and product quality, there remain opportunities to develop innovative forms of DNA. Touchlight is committed to the development of next-generation DNA forms that can further improve biomanufacturing and unlock new possibilities in advanced therapeutics.
Leveraging Touchlight’s established synthetic DNA production capabilities to enable simplicity and scalability of manufacture, Touchlight has developed MegaBulb DNA (mbDNA) — a novel, circular, single-stranded DNA (ssDNA) template for CRISPR gene editing.
Designed to combine the increased editing efficiencies achievable with ssDNA templates with the improved viability and consistency enabled by synthetic DNA, this circular ssDNA has improved stability and the ability to incorporate multi-kilobase sequences, far exceeding the capabilities of traditional viral vectors. mbDNA also offers enhanced targeting specificity, facilitates nuclear trafficking, and can be used with any targeted nuclease, making it a versatile tool for precision gene editing.
mbDNA has been engineered to minimize toxicity, which allows for the use of higher DNA concentrations during the knock-in process while preserving cell viability. In its early applications, mbDNA has shown remarkable efficacy, achieving knock-in efficiencies of 75% in primary T cells — rivalling the performance of AAV vectors. This extends to outperforming commercially available linear ssDNA templates, achieving fourfold greater rates of homology-directed repair (HDR).
Consistent editing profiles across different blood donors and efficacy across diverse cell types underscore mbDNA's potential for personalized medicine, particularly ex vivo autologous cell editing.
Leading the Genetic Medicine Revolution Today and Tomorrow
As the biotech landscape evolves, Touchlight has emerged not merely as a participant but as a pioneer, having been among the first to explore alternative DNA production methods that transcend the limitations of traditional pDNA. Touchlight's innovative approach is distinguished by several formidable advantages. First, the company boasts a vast and growing repository of data affirming the superiority of enzymatically manufactured dbDNA over traditional plasmids, as well as other enzymatic DNA approaches, in terms of yield, purity, and other critical metrics. Second, Touchlight's simple, elegant and efficient production process, characterized by its scalability and rapidity, enables not only swift GMP manufacturing but also significant reduction of overall costs. Third, Touchlight enjoys clear regulatory advantages over other forms of synthetic DNA; it has established a DMF, routinely produces GMP material at scale, and is actively supplying DNA and regulatory dossiers to clinical trials, with a pivotal study slated for later this year. Underpinned by significant operational experience and led by seasoned executives, Touchlight is uniquely positioned as the leader in the synthetic DNA market today and is poised to play a central role in realizing the full potential of the genetic revolution, from the first-line defense against emerging pathogens to the development of truly personalized medicines.
