Cenk Sumen, PhD, is a researcher.
Biopharmaceuticals' life cycle is driven by safety, affordability, and timeliness to market. Process optimization is critical to shortening the development cycle and reducing the cost of goods, tout while respecting industry safety standards.
Cell lines that express specific proteins during biopharmaceutical development must be created, usually by transfection. Employing transient protein expressionrather than stable protein expressionduring further steps of the development process will increase productivity.
Typically, therapeutic developers utilize transient protein expression only during the discovery phase. They invest early in stable cell line development before evaluating drug performance and capacity to manufacture at scale.
During testing and validation, researchers typically evaluate a key candidate for efficacy, toxicity, and manufacturability. If the protein fails, companies must invest more time, effort, and money to develop an entirely different stable cell line because the initial cell line isn't intended for another substance.
Although stable cell lines have the purpose of providing reliable, long-lasting protein production, establishing them requires significant effort and time, posing a threat to industry development and limiting pipeline expansion. In the meantime, patients are waiting, competitors are moving forward, and the company is saving cash.
Transient transfection is relatively inexpensive but straightforward. It is also possible that a transient cell line to produce adequate material for testing is much quicker, taking weeks rather than months. This helps sponsors companies rapidly assess new molecules and choose which ones to take forward into the clinic.
The first phase of this series of monoclonal antibodies can last ten years or more, and it costs around $1 billion. Failure rates can be greater than 90%. The biotech industry is urgently need to improve therapeutic protein discovery, and adopting more effective cell lines can be a critical step in that process.
The fact that life sciences research moves slowly is a given, but when world events brought a fresh sense of urgency, COVID-19 vaccinations were developed with a new speed. A process that had previously taken 10 years was completed in less than 2. This proves that research and development can respond with agility to a pressing patient need.
This new focus on speed is particularly important for corporations working in novel spaces where being first to market offers unique advantages. Patients with limited therapeutic options may finally get a chance at treatment. Smaller patients can benefit from this approach.
Transient transfection is such a game changerit prioritizes speed and consistency. Electroporation is applied to gently relax the cell membrane, reducing the genetic payload, while allowing quick cell recovery. Newly engineered cells are available in just a couple of weeks, and laboratories can produce sufficient quantities of several candidate proteins in parallel for testing.
This technique offers researchers new opportunities to fail quickly, whether it be abandoning fruitless options quickly, or turning to potentially successful options. This is a critical paradigm shift. When relying on stable cell lines, companies must make substantial long-term investments just to produce them.
Laboratorys have the ability to rapidly iterate when a component fails. If a sample fails, labs may move quickly to the next molecule and, if necessary, the one after it. The labs are no longer stuck for months in search of constant transfection.
Companies are able to expedite decisionmaking and significantly reduce costs owing to this rapid timeline. After the new candidate is verified safe and effective, labs can stably transfect a cell line to complete optimization and move into commercial production.
Even if the actual process fails, established practices may be difficult to follow. Occasionally, individuals and organizations are reluctant to adopt new ideas.
In the early stages of biopharmaceutical development, transient transfection has already been widespread, on a small scale. Electroporation's consistency and reproducibility are beneficial to facilitate the transition to larger-scale production.
The regulatory pathway is another important issue. Many believe that stashed transfected cell lines provide the best, perhaps the only, path to regulatory approval. However, there is precedent in vaccinations, many of which utilize transient transfection all the way through to commercial production.
Electroporation is being used in FDA-approved cell therapy trials, which are, in many ways, more complex than bioproduction. There are also commercially available therapeutics being made in transient cell lines. The technology has been proven effective and has a viable regulatory path.
Transient transfection may be beneficial to virtually any biotech company, but this technology might be beneficial for biotech startups and contract development and manufacturing organizations (CDMOs).
CDMOs must constantly scan the horizon for competitive advantages. They have a greater traction while improving production and costs. For startups, the problem of improving market time is ever present, and transient transfection can be an integral part of the solution.
We will need to take some serious risks when it comes to transient transfection. It is proven technology that is poised to expand, and in the end, the benefits to patients may be beneficial.
Cenk Sumen, PhD, is MaxCyte's chief scientific officer.