New Trends in Viral Vector Production and Cell Culture Technology Optimize Your Workflow | Corning

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Viral vectors, which use modified viruses as vehicles to access genetic and cellular material, are one of the most commonly deployed tools in the search for a vaccine for SARS-CoV-2, the virus that causes COVID-19.

But COVID-19 didn't put viral vector research on the map. Scientists had been increasingly using viral vectors in therapeutic research well before the coronavirus pandemic, as their use in gene therapy and cell therapy has proven promising. Now, those same applications are being repurposed to develop a coronavirus vaccine.

However promising they might be, viral vector workflows come with inherent challenges in scale and process. Fortunately, technology is evolving rapidly, and new solutions to simplify viral vector bioprocessing are continuing to emerge.

Viral Vector Production Workflow

Producing viral vectors typically follows a six-part workflow:

  1. Generation of the starting material
  2. Cell expansion
  3. Virus propagation
  4. Viral harvest
  5. Purification
  6. Aseptic fill and finish

Choosing a Cell Culture Technology

The optimal choice of technology platform for each of the workflow steps depends on the viral vector being produced and the required scale of the bioproduction. One question associated with cell expansion is whether to grow the cells in an adherent or suspension platform. That decision isn't always straightforward.

"There's a big debate in the field right now about which is the best way to produce viral vectors: with adherent cell culture platforms or with suspension platforms," said Austin Mogen, PhD, a field application scientist at Corning Life Sciences. "Adherent platforms have been well-established for many years, but we are seeing increasing popularity in suspension platforms for multiple reasons. Ultimately, the choice will depend on many factors, including time required for process development, scale, cost, and development of new technologies."

Utilizing adherent vessels at large scale can be challenging due to the historic manual nature of processing adherent cell culture. However, they are also considered the more optimized choice for many cell lines utilized in viral vector production, typically producing higher viral titers than suspension platforms. On the other hand, suspension platforms can provide benefits of scalability and process control, such as implementation of a bioreactor.

Advances in Closed-System Adherent Cell Culture

One way to get the best of both worlds is to work with a closed-system and integrate automated solutions into your workflow. This can unlock scalability while limiting variability and mitigating the contamination risk of open cell culture manipulations.

"Generally, a single vessel is not enough to produce the amount of viral vector that's needed," Mogen said. "That's why many researchers have turned to Corning® closed-system solutions that use tubing manifolds to connect multiple vessels. This allows decreased processing time, while also allowing you to generate much more of the viral vector without substantially increasing the aseptic risk."

Gas Permeability for High-Density Cell Growth

Vessels such as the Corning HYPERStack® come standard as a fully closed system and utilize a gas-permeable film to support high-density cell growth within a smaller footprint. This can maximize limited incubator or warm room space, which is another inherent challenge of the viral vector workflow. Ensuring optimal gas exchange means that the cells get the oxygen and carbon dioxide they need, and typically produce higher viral vector titers when compared to other stacked vessel technologies. According to Mogen, "Many of our customers are currently using the HYPERStack vessels to produce viral vectors for their clinical programs."

Streamlining Processes Through Automation

New automated solutions can speed up the processing time for modular adherent vessels such as Corning CellSTACKs® and HYPERStacks. The Corning® Automated Manipulator Platform semi-automates adherent bioprocess workflows and makes it easier for researchers to stay on adherent platforms.

"This essentially decreases processing time and process variability," Mogen said. "That's a big concern when you're working with multiple vessels. Automation removes the subjective component of individuals handling vessels so that it's more consistent and potentially safer, given the ergonomic strains and workplace hazards of lifting heavy vessels."

The Future of Viral Vector Research

The efficient production of viral vectors has opened new opportunities for researchers involved in a variety of focus areas including cell and gene therapy, and the development of new vaccines. Although COVID-19 didn't launch the interest in viral vectors, it has accelerated the urgency to expand understanding and expertise in this exciting field.