Applying synthetic biology to remove p24 impurities from the lentiviral product streams used in T cell engineering

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Biopharmaceutical companies must contend with the bioprocess challenges posed by the presence of free, soluble p24 protein, also known as capsid or CA, in the lentiviral process streams used for cell and gene therapy products and their development. Free p24 has a propensity to form aggregates, can compromise the efficiency of gene transfer to target cells and may also confound p24-based estimates of virus production. Engineered, self-inactivating lentivirus is a key tool for both direct, virus-mediated gene therapy and for the ex vivo transduction of mammalian cells resistant to other methods of genetic modification, such as stem cells. With the emergence of T cells as a major new therapeutic product class, the importance of lentiviral engineering has only increased This project will establish if flexible linkers can be used to significantly alter the molecular weight and membrane-association properties of p24 so it no longer manifests to the same extent as a free, soluble protein in lentiviral product streams. Flexible linkers have a lengthy track record of application in fundamental research and biotechnology. Critically the project aims to achieve this p24 removal whilst preserving the performance of engineered lentivirus as a tool for efficient gene transfer to therapeutic T cells.