19 May 2022
The incredible success of the two mRNA vaccines against COVID-19 sparked a surge of interest and investment in this new therapeutic modality. And because mRNA is infinitely programmable, scientists are now working on deploying it towards fighting many other diseases. Our customers have already embarked on this second wave, developing mRNA drugs to treat bacterial infections, rare genetic diseases, cancer and more.
This pandemic-inspired mRNA gold rush has raised challenges, however, boosting the demand for new, integrated technologies that can improve research, development and manufacturing. For example, we know how to deliver mRNA to some tissues of the body, the liver primarily, but researchers are striving to improve delivery vehicles so they can get mRNA therapeutics where they need to go to be effective against a wide range of illnesses.
Pharmaceutical companies that are pursuing mRNA can address these challenges by partnering with science and technology companies that provide support at every stage of the R&D process. This convergence of technological capabilities will fuel new opportunities for mRNA developers beyond infectious diseases.
Building a Strong mRNA Backbone
The life sciences companies of Danaher are setting the template for end-to-end creation and manufacturing of mRNA medicines. This starts with Integrated DNA Technologies (IDT), which develops custom DNA and RNA oligonucleotides. IDT’s gBlocks™ Gene Fragments aren’t just used for traditional genetic cloning. They can also be used as templates to make mRNA.
The potential for this technology extends far beyond mRNA vaccines against COVID-19. Say a drug developer wants to develop personalized mRNA vaccines that fight cancer based on genetic mutations found in individual patients’ tumors. Essentially, they would be using mRNA to teach a patient’s immune system to fight his or her cancer by recognizing and killing cancer cells with those mutated genes. With gBlocks™, it’s possible to make an mRNA template for that vaccine in as little as a week.
The rise of mRNA has increased the demand for some tools that have moved beyond the laboratory and are now needed for large-scale manufacturing of genomic medicines. Take plasmid DNA, for example. DNA vaccine manufacturers need plasmid DNA to deliver the genetic code of the target virus into the body, which then translates the genetic sequences and produces the viral proteins that elicit an immune response. Plasmid DNA is also used as a raw material for the production of viral vector-based gene therapies and mRNA medicines.
As the leading provider of high-quality plasmid DNA, mRNA and recombinant proteins necessary for vaccines, gene and cell therapy, gene editing and diagnostic applications, Aldevron has supported many genomic medicine developers over the years. For instance, Aldevron collaborated with Moderna for over a decade. And last year, Moderna expanded their partnership with Aldevron, who supply them with the plasmid DNA they need to serve as the genetic template for generating the COVID-19 mRNA vaccine and other investigational programs in their pipeline.
Furthermore, Aldevron offers a plasmid DNA backbone that can support a wide range of lentiviral and adeno-associated viral (AAV) delivery vectors. Aldevron’s NanoplasmidTM platform is ideally suited for mRNA developers, as it is smaller than standard plasmid backbones and is free of antibiotic markers. Those characteristics help improve manufacturing and can significantly reduce the cost and time of developing mRNA medicines. In fact, Aldevron can work with manufacturers of mRNA-based medicines early in the research process to design the ideal plasmids for their mRNA projects.
Simplifying and Optimizing Manufacturing
For mRNA to reach its full potential, the biopharma industry must also simplify and optimize manufacturing, not only of the nucleic acids but also of the lipid nanoparticles (LNPs) that are used to protect and deliver them. LNPs are complex; in the early days, developers of mRNA vaccines and other genomic medicines had to hire specialists trained in the art of making them—and there weren’t enough of those specialists to meet the growing demand. The process of making LNPs by hand is cumbersome and prone to error. So another Danaher company, Precision NanoSystems (PNI), stepped up to provide an automated solution.
PNI’s NanoAssemblr® microfluidic manufacturing platform makes it possible to take nucleic acid and lipid formulations for mRNA drugs and put them into one end of a device that’s small enough to fit on a lab workbench. Press a button, and out comes well-formed, stable LNPs. Furthermore, owing to the scalable nature of PNI’s microfluidics, the production volumes of LNPs can be easily increased. It’s so simple that one of PNI’s customers reported that they’re shaving 10 months off the development time of every drug candidate they have in their pipeline. That translates into cost savings. And it greatly simplifies mRNA development, bringing it well within reach of researchers that may have shied away from it before.
The COVID-19 vaccines were only the beginning of the mRNA revolution. In the second wave, I predict we’ll see this modality used not only to prevent other infections, but also in the context of gene editing to cure diseases. We’ve seen a convergence of innovation that has resulted in better mRNA formulation, stabilization and delivery. But we’re just at the beginning of that convergence. We need to build on it to realize the full potential of mRNA.
Sadik Kassim, Chief Technology Officer, Genomic Medicines
Sadik Kassim is Chief Technology Officer for Genomic Medicines for the Life Sciences companies of Danaher Corporation. Sadik is responsible for identifying and driving the optimal path for implementation of genomic medicine R&D strategies across Danaher’s operating companies. He has held several leadership positions in biotechnology companies and is experienced in a range of genomic technologies, including AAV-based gene therapy, CAR-T cell therapies and CRISPR gene editing.Print
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