E1 - Nonviral Therapeutic Gene Delivery and Synthetic/Molecular Conjugates
1716: A Novel, Synthetic DNA Alternative for mRNA Manufacturing
Type: Poster Session
Poster Board Number: 1716
Presentation Details
Session Title: Friday Posters: Nonviral Therapeutic Gene Delivery and Synthetic/Molecular Conjugates
The emergence of messenger RNA (mRNA) as a transformative platform for gene therapy and vaccine applications, especially in the wake of the COVID-19 pandemic, has ignited a quest for innovations in mRNA production. A pivotal challenge in this space revolves around the choice of a DNA template for in vitro transcription (IVT) to generate mRNA. While bacterial-derived plasmid DNA has been the go-to template, its utilization has presented a significant bottleneck in mRNA manufacturing due to issues of cost, turnaround time, and purity concerns associated with the incorporation of bacterial-derived sequences into the final mRNA product.
We have developed a novel, optimized synthetic linear double-stranded DNA with customizable hairpin-ended structures designed to serve as an alternative to plasmid DNA for mRNA production, completely devoid of any bacterial elements. The platform offers unparalleled advantage in terms of scalability, delivering high-fidelity, high-yield, and high-purity DNA within a remarkably brief timeframe.
Here we show that our synthetic DNA is a versatile template for in vitro transcription that accommodates a diverse range of mRNA designs, and encompasses variations in length, capping technologies, and degrees of chemical modification. The use of our synthetic DNA for IVT affords significantly higher mRNA yields as compared to conventional plasmid DNA, while exhibiting comparable integrity, purity and levels of dsRNA contaminants. Furthermore, the functional activity of mRNA produced from our novel DNA is equal or superior to benchmark mRNA synthesized from plasmid DNA. The implications of these results underscore our novel DNA as an innovative and robust solution to overcome the bottleneck encountered in mRNA manufacturing.
Plain Language Summary
The messenger RNA (mRNA) has become a great tool for gene therapy in the last few years. However, a current bottleneck is the sourcing of the DNA template used as input material.
We have developed a novel synthetic linear double-stranded DNA with customizable hairpin-ended structures and without bacterial sequences for use in mRNA manufacturing. Our production process is a one-pot, enzymatic, cell-free, scalable reaction. In this work, we show the capabilities of our synthetic DNA by using genes of various lengths to generate mRNA through in vitro transcription using different capping technologies, and various degrees of chemical modifications. We show that our novel DNA is an innovative and robust solution to overcome the bottleneck encountered in mRNA manufacturing.
Gustavo Lou, David Wilson, Ivana Pastierikova, Luca Distefano, Marco Guarrera, Alexander Pekarsky, Jorge Omar Yanez Cuna, Joel de Beer
Anjarium Biosciences AG, Schlieren, Switzerland"
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