By Daniel G. Bracewell, Professor of Bioprocess Analysis, UCL Department of Biochemical Engineering
Personalized medicine stands to be a revolutionary transformation to patient care. The traditional methods for drug development will no longer be applicable, as this new approach to modern medicine focuses on a more targeted form of patient treatment. However, the models used to produce large batches of drug product are not economical on a smaller, individualized scale. Therefore, as the industry explores the possibilities of precision care, it must consider alternative manufacturing platforms that can make these ideas a commercial reality. To ensure these medicines can be affordable, improved agility and productivity in process design is critical.1
One possibility for doing so is the use of cell-free synthesis (CFS) systems, which were first introduced over 50 years ago as a tool to investigate genetic code as well as for the synthesis of proteins for structural biology. Also known as in vitro transcription/translation (IVTT), CFS is a method for protein synthesis through translation performed with biological components but without the use of living cells. Instead, the preparation or the growth of the cells is separated from the reaction itself using centrifugation, preserving the ribosomes, and transcriptional machinery of the cell. The cell-free reaction is then combined with an energy source and the DNA of the protein to be expressed. It may be necessary to add other cofactors and supplements, such as tRNA synthetases, translation initiation, and elongation factors.
Separating the biological reagent preparation from the cell-free reaction makes CFS systems well suited to manufacture at the point of treatment, improving patient access, particularly to communities without established distribution networks. Yet, transitioning to a more efficient model for the future of medicine faces several challenges due to restrictions in today’s regulatory, development, and manufacturing environments.