Surges in the research, development, and supply chain capabilities for new vaccines to combat the COVID-19 pandemic may be key to accelerating clinical translation and patient access to a whole new class of advanced therapies. As we inch toward a post-pandemic world, biologics researchers and manufacturers hope to leverage the vaccine infrastructure established thus far and expand it through interdisciplinary collaboration to bring novel therapeutics — cell therapies, gene therapies, and regenerative treatments — safely and cost-effectively to the people who need them.
According to biomedical engineering associate professor Krishanu “Kris” Saha, platform technologies — namely newly engineered mRNA, viral vectors, and proteins — are fundamental components to vaccine and therapeutic development alike. These technologies can be biologically edited to address different strands of information, making them programmable for vaccine development and for personalized cell and gene therapies used to treat a wide range of disorders: from sickle cell disease to cystic fibrosis.
“In one sense, the vaccines are simply different codes of what engineers want to program in to build novel antigens, including bits of emerging variants, within the body. Then, the immune system takes it from there and produces immunity for the individual,” Saha says. “In many ways, gene/cell therapy is similar, coding for therapeutic proteins within the formulation rather than viral antigens.”
Because of this interchangeability, merging the cell and gene therapy world with the vaccine development world could dramatically increase the reach of various cell and gene therapies, including CRISPR, while augmenting our preparedness for future public health crises. And, given the wide array of lessons learned in the wake of the pandemic — from research and development to supply chain solutions — there is a wealth of information available to utilize. The major problem with this: the vaccine and cell and gene therapy worlds are still relatively siloed. According to Saha, the development of public-private partnerships, maturation of cyberinfrastructure, and the expansion of workforce training paired with even more biomanufacturing flexibility could help bridge this disconnect, particularly if driven through cross-disciplinary efforts.
“We need to increase our manufacturing capacity to allow for interchangeability, so that we can switch between products readily and scale up when the demand skyrockets, like we have seen in the past year,” Saha says. “There is an opportunity to incorporate sensing and data science and genetic engineering into these manufacturing processes and enable this flexibility to scale out and scale up.”
Industry — specifically, companies like Aldevron and Catalent, biologics manufacturing companies in Madison — can play a major role in filling some of these gaps, according to Saha. Aldevron, in particular, specializes in manufacturing all kinds of advanced therapeutics, including both vaccines and cell and gene therapies, which can be crucial to uniting these sectors.
“What we’re talking about is how to deliver genetic cargo with vaccines and potentially curative cell therapies or gene therapies,” Tom Foti, the President of the Protein Business Unit at Aldevron, says.
“In theory, we are moving genetic medicine towards the idea that we can solve the problem at the root cause and not just deliver drugs that treat symptoms. That’s the most exciting part. The idea is to do this safely and cost effectively.”
In this sense, industry partnerships are essential not only to promote information sharing for biologics, but also to foster their commercialization and dissemination. According to Bill Murphy, Harvey D. Spangler Professor & H.I. Romnes Faculty Fellow of biomedical engineering, combining perspectives from both the public and private sectors helps streamline the supply chain process and encourage even more innovation. As seen during the pandemic, however, efficient delivery of these therapeutics after their creation is a challenge. Various supply chain barriers exist, and mass production challenges are multifaceted even when academia and industry are united.
Before therapeutics are even able to be produced, regulatory hurdles, a stringent, though necessary process to ensure safety, can take a long time to overcome, Murphy says. After that, the value chain involved with actual production begins. According to Foti, each step within the production process requires a variety of supply chain considerations.
A notable supply chain barrier prevalent throughout the pandemic has been the overall instability of mRNA. While stabilizing the mRNA with lipid nanoparticles just to deliver the therapeutic into the body is a challenge, keeping the mRNA viable during long-term storage creates another issue for mass production and distribution. The need for cold storage using refrigerators, freezers, and dry ice to address this issue has spurred both creativity and adaptability from biomedical engineers.
Adhering to the challenges of COVID-19, for Murphy’s team, meant pivoting existing projects to address this difficulty. Because his lab has been working to stabilize molecules in extreme environments for nearly a decade, transitioning his focus to long term mRNA storage was a natural step during the pandemic. Murphy hopes, through the strong partnerships within the Forward Bio Institute, an institution he directs, these research advancements can be quickly applicable to the market.
“We are effectively trying to catapult [research] out of the institution and into the hands of the folks who can broadly disseminate them and affect society, which is really the fundamental concept behind the Wisconsin Idea,” Murphy says.
This research, enabled in part by seed funding from the Grainger Institute for Engineering, utilizes inorganic, biomimetic materials to stabilize mRNA at room temperature. Because of the overlap in applicability of platform technologies like mRNA delivery, however, this kind of research, too, could be relevant for a multitude of therapies, even in a post-pandemic world.
“The mRNA therapeutics are being used in a couple of the prominent COVID vaccines, but those are only among the initial products that are based in mRNA technology: there are actually multiple pipelines of therapeutics that are based in mRNA delivery,” Murphy says. “There is also potential to use our approach to stabilize protein delivery technologies, and even to use related concepts to stabilize cell therapies as well. So, we think the general idea of using materials to stabilize biologics ends up having an impact that goes way beyond our initial mRNA therapy work.”
As the world begins moving forward, the consistent dedication to exploration within academia paired with the supply chain capabilities and expertise of industry has proven to be forefront in solving global, grand challenges. Interdisciplinary efforts have been incredibly impactful in the fight against COVID-19. For advanced therapeutics, this collaborative mindset can help solve existing issues while better suiting us to face those to come.
“We have learned that we can quickly respond to something through innovation in a way that has never been done before. And we’ve learned that sometimes we put constraints on how we do things because of the historical paradigm and the way we think about problem solving,” Foti says. “We can look at things through a new lens and a new paradigm, and we can scale and produce these biologicals very quickly.”
Author: Katie Amdahl