Conditional Immortalization
Immortalized cell lines offer the possibility of an inexhaustible supply of cells that can be used as models of animal or human tissues. However, a major limitation of current technology is that the available models are almost invariably poor representations of cells found in intact tissues. One major reason for this is that the process that allows the cells to become immortal also has an impact on the characteristics of the cell.
Lonza overcomes this limitation using a temperature dependent, conditional immortalization approach utilizing Large T-Antigen that allows the immortalization to be reversed and the cells to revert to their original characteristics. This allows development of cell lines from a wide range of human and animal tissues, and of novel models relevant to drug discovery based on lines from people with particular diseases.
Use in Drug Discovery
During recent years increased pressure has been placed on drug development teams to deliver drugs to the market that meet the proscribed claims, have no side effects, and perform no matter the patients genetic background. To add to the challenge, drug development resourcing is not growing at the same rate as external costs to validate new drugs for the market. Now more than ever drug discovery researchers need tools that facilitate HTS screening of cells earlier in the drug discovery process, eliminate poor drug candidates early and focus on more promising candidates.
To discover a new drug, researchers must evaluate a large number of compounds for efficacy and toxicity. Several accepted models exist using animals or cells, but all have inherent limits for quick evaluation using high throughput screening techniques and require species extrapolation to evaluate the data.
Live animal models yield a rich supply of data but are not cost effective for high throughput screening. Non-immortalized, primary cells may best represent normal physiology, but are typically not available in the large, uniform quantities needed for HTS applications. Though conventionally immortalized cell lines can divide indefinitely into large homogeneous cell populations needed for HTS applications, they do not behave like normal cells. Conditional immortalization allows, at a permissive temperature, production of high volumes of uniform cell populations. By changing the culture temperature the cells stop dividing, irreversibly, allowing for differentiation so that the cells can express normal function and phenotype once again.
