Gene editing is transforming the treatment of inherited diseases, but efficient and precise gene insertion has often come at the expense of cell viability, stem cell fitness, and long-term durability. In this executive summary, Touchlight explores how Megabulb DNA (mbDNA), a proprietary circular single-stranded DNA HDR donor, addresses key limitations associated with traditional viral donor systems such as AAV, including toxicity, payload constraints, manufacturing complexity, and safety concerns. The summary highlights preclinical and translational data demonstrating how mbDNA is engineered to support high-efficiency genome editing while minimizing cellular stress and preserving the long-term function of hematopoietic stem and progenitor cells (HSPCs).

Drawing on independent research from the University of Padova and CIEMAT, the report examines the performance of mbDNA in clinically relevant stem cell models, including its ability to support targeted gene insertion, maintain cellular function, and preserve genetically corrected cell populations over time. It also outlines how non-viral HDR donor technologies may enable safer, more scalable, and commercially viable gene therapy workflows, with compatibility across emerging delivery platforms such as electroporation and lipid nanoparticles (LNPs).

Download the full executive summary to explore the data behind mbDNA and its potential to help redefine the future of precision gene editing and genetic medicine.

Non‑viral gene editing is emerging as a compelling alternative to viral vector–based gene therapy for hematopoietic stem and progenitor cells (HSPCs), offering the potential for precise, targeted gene insertion while avoiding the manufacturing complexity, payload limitations, and cellular stress often associated with viral donors. However, achieving efficient homology‑directed repair (HDR) in HSPCs while preserving cell viability, fitness, and long‑term function remains a key challenge.

In this webinar, we explore recent advances in non‑viral knock‑in strategies using Touchlight’s mbDNA (MegaBulb DNA)—an enzymatically produced, circular single‑stranded DNA template designed to enable highly efficient HDR with minimal toxicity. Presenters will share data demonstrating robust targeted integration in primary human CD34⁺ HSPCs across a range of mbDNA doses, using co-electroporation with CRISPR/Cas9 RNPs and compared to AAV and plasmid DNA controls. These results highlight unrivaled knock‑in efficiencies alongside preserved cell viability and recovery, underscoring the potential of mbDNA as a next‑generation HDR donor format to replace the incumbent viral vectors. Studies evaluating the impact of this system on the engraftment potential of edited HSPCs are currently ongoing. The speakers also outline how mbDNA can be combined with emerging lipid nanoparticle (LNP)-based delivery systems, pushing the frontiers of HSPC gene editing.

The session also discusses how non‑viral mbDNA‑based platforms can be integrated with emerging genome engineering and delivery strategies to enable safer, scalable, and lineage‑oriented gene therapy workflows. Register to watch the session and gain practical insight into how non‑viral HDR donor formats can help overcome key limitations of viral approaches and support the development of more precise, effective therapies for inherited hematopoietic diseases.

Key learning objectives:

• Learn why non‑viral gene editing is gaining momentum for use in blood stem cells and how it compares to traditional viral approaches
• Discover how mbDNA can be used to insert genes more precisely into human stem cells while maintaining cell health and viability
• Explore how new non‑viral gene editing and delivery strategies could enable safer, more scalable gene therapies for inherited blood disorders

Watch the webinar to see the data in action.

Click here to download the one-pager 

Touchlight’s Chief Scientific Officer, Dr. Jill Makin, discusses how the rapid evolution of advanced therapeutics is reshaping the industry, and why cell‑free DNA is has emerged as a foundational technology for the next wave of therapeutic innovation. With pipelines expanding across gene editing, non-viral gene therapies (NVGT), and viral vector–based therapies, developers are facing unprecedented pressure to improve speed, affordability, and manufacturability.

Moderated by Will Downie, Touchlight Non-Executive Director and Operating Partner with Advent International. He is the former Chief Executive Officer of both Argenta and Vectura.

Topics will include:

• Why cell‑free DNA is becoming essential infrastructure for modern genetic medicines, and how it addresses key bottlenecks in purity, scalability, and regulatory expectations.
• How gene editing and NVGT programs depend on cell‑free circular single-stranded DNA to unlock their full therapeutic promise.
• How viral vector programs can dramatically reduce cost-of-goods (COGS) and accelerate timelines by replacing plasmid‑based workflows with cell‑free DNA.

This application note evaluates the in vivo performance of Touchlight’s doggybone DNA (dbDNA) compared with conventional plasmid DNA when delivered using Sartorius Polyplus non‑viral delivery reagents. The study investigates how dbDNA influences protein expression levels and durability across multiple tissues following both intravenous and intramuscular administration in mouse models.

Cell and gene therapy has long relied on plasmid DNA (pDNA) to power clinical innovation. But cell‑free DNA is already in use, treating patients, and rapidly becoming established as a scalable, consistent, and cost‑efficient alternative. As manufacturing demands grow, developers are reassessing which DNA format best supports speed, reliability, and future‑proofing.

Download this Q&A to get insights from Touchlight’s CSO Jill Makin, Ph.D., Chief Scientific Officer, on the advantages of cell-free DNA, and the considerations developers should make when selecting a platform.

Plasmid DNA has long been the workhorse of cell and gene therapy — supporting countless clinical programs and enabling many of the field’s most important breakthroughs. At the same time, cell‑free DNA has already reached clinical use, where it is increasingly adopted to treat patients and now operates alongside plasmid DNA within today’s manufacturing landscape. How can companies optimize and select the right DNA technology to meet evolving demands for scale, consistency, speed, and cost of goods?

Download the webinar to watch as two leading DNA experts have a candid debate with real-world data exploring where plasmid DNA continues to excel, where cell-free DNA is uniquely positioned, and how both platforms will shape the future of the cell and gene therapy landscape.