Gene therapy is a treatment strategy that addresses a disease condition by introducing new genes into cells. In contrast to drug treatments or surgery, this technique is designed to address the root cause of the pathology. The process often begins following a positive diagnosis for a disorder approved for treatment by gene therapy.
Viral vectors are commonly used in gene therapy to safely transport a therapeutic gene to the target cells. To ensure high efficacy and patient safety, rigorous vector production and characterization is crucial.
Scientists grow cells which produce gene therapy vectors in a bioreactor. During the process, cell growth and viability is monitored, along with the surrounding media and metabolites. Maintaining optimal, consistent growth parameters can maximize production and help mitigate resource waste.
Once the cells have adequately grown, the cells are quickly and reliably separated from cell culture media with a high performance centrifuge. Viral vectors may be secreted into the media or retained in the cells. In this scenario, we will focus on the cells.
Cells within the pellet are resuspended and then lysed through mechanical or chemical methods, which releases the gene therapy vector. For low shear and minimal product loss, cellular debris can be removed through high performance centrifugation, where BioSafe systems ensure operator and sample protection.
Next, particle separation through density gradient ultracentrifugation provides high yields of capsids with high purity. For both step and continuous gradients, the desired viral vector and contaminants can be found at discrete locations corresponding to their respective densities. Typically, full capsids are desired and these more dense vectors are found lower in the gradient.
The band of interest may then be extracted. A small amount can then be analyzed for quality control and characterization, while the majority of the liquid is packaged into vials, ready for shipment.
Quality control is crucial throughout gene therapy production. High-resolution native state analysis with analytical ultracentrifugation confirms that the finished product consistently contains mostly full capsids. AUC is the industry standard technique to quantify packaging efficiency of viral vectors.
After passing the QC inspection, the gene therapy is shipped to be administered to the patient.
Given current pace, the future of gene therapy looks bright. Continued expansion of use will compliment drugs or surgery for many debilitating disorders. To learn more about gene therapy and the ways that Beckman can facilitate its production, visit beckman.com/resources.