Cell and Gene Therapy
TLA analyses have increasingly been adopted in the quality control of genetically engineered cells towards the manufacturing of cell and gene therapy products. In fact, TLA technology can be applied in various stages of the cell line development process towards the manufacturing of gene therapy medicinal products (GTMPs).
QC in the upstream process
In the upstream process, TLA technology enables the characterisation of genetic stability and clonality of producer cell lines (e.g. production of therapeutic viral vectors). Depending on the goal, TLA can support in the:
- optimisation and validation of new technologies (to help assess the most robust technology to be used in the final/actual production process);
- selection of clones (stable and clonal cells are expected to continue sharing the same integration site(s) and genetic alterations, should those accompany transgene integration);
- clonality and genetic stability (to assess the clonality and genetic stability of daughter cells resulting from a master cell bank).
QC in the downstream process
In the downstream process, TLA can map viral integration sites.
Furthermore, TLA can quantify the number of correct and incorrect integration events at the intended location. For instance, TLA-based targeted transgene and integration site sequencing has been applied to:
- assess the targeting of a CAR to the TRAC locus (see publication MSKCC);
- completely sequence the HIV genome in a patient's blood sample (see Nature publication);
- evaluate transfected/transduced immune cell samples (e.g. T- and B-cells). For example, towards the development of CAR-T cell therapies.
Click here to watch a recording of our most recent webinar and learn more about the relevance of TLA technology in the production of cell and gene therapy products.