What is Cell-Based Assay?
Cell-based assay or cellular assay is a bioanalytical method that is commonly used to assess the biological activity of substances such as biotherapeutics by measuring their functional response in a cell-based culture assay. They help to evaluate cellular processes such as viability, apoptosis, growth, proliferation, and various regulatory networks and diverse functional aspects of cells. Using cell-based assays, it is possible to interrogate different cellular processes to get an insight into what is happening inside the cells. Thus, these assays offer a wealth of information and are indispensable tools in biomedical research and drug discovery. In drug discovery, these assays can help screen drug candidates for potential targets, assess cytotoxicity and biological activity, and understand biochemical mechanisms, cellular processes, and off-target interactions.
Cell-based Assays have multiple advantages over their traditional biochemical counterparts. In contrast to biochemical assays using proteins or cell lysate, cell-based assays determine different cellular parameters in living or fixed cells. Being a complex system with the capacity to model cellular behavior accurately, cell-based assays produce biologically relevant and reliable data. They can simultaneously assess compound characteristics and are more physiologically relevant.
Types of Cell-Based Assays
There are different types of cell-based assays based on their applications. Some commonly used assays are cell viability assay, cell proliferation assay, cytotoxicity assay, cell senescence assay, and cell death assay. Cell viability assays help to estimate the ratio of live and dead cells. This assay is beneficial in determining the effect of potential drug candidates on cells by monitoring diverse parameters such as cell redox potential, cell membrane integrity, cell enzyme activity, etc. Cell proliferation assays help to monitor cell replication with time, i.e., the rate of cell growth. Cell proliferation is a crucial cellular process that ensures proper growth, development, and maintenance of organisms. Cytotoxicity assays help to determine the dead and live cell populations in a sample. Thus, it can be used to evaluate the toxicity of a drug candidate on a cell population. Cell senescence assays help to monitor cell health by assessing biomarkers associated with the cellular process of senescence. Cell death assays help study major cellular processes such as apoptosis, autophagy, and necrosis of cells. In addition, there are other cell-based assays such as protein degrader assay, migration assay, cytokine assay, and reactive oxygen species assay.
Cell-based assays are also used for immunotoxicity and immunogenicity analysis. Drugs, biologics, in particular, can evoke and mount immune responses upon administration and are thus a cause of concern in drug development. Animal models are increasingly used to study immunogenicity of biologics. However, in vitro animal models often fail to predict immune responses that might be elicited in humans. Cell-based assays using human cell lines can closely mimic actual physiological conditions and help in Immunogenicity Analysis.
Since cell-based assays such as cell-viability assay, cell proliferation assay, cell death assay, etc. help to evaluate cell functioning, they are also referred to as cell-based functional assays. These assays can be coupled to different readout systems to obtain information crucial to drug discovery.
In addition to cell-based functional assays, cell-based screening assays are frequently used in drug discovery. Most of the high-throughput screens currently used in drug screening are cell-based assays. In drug discovery, cell-based screening assays can help to screen targets and identify hits. They are well suited to screen targets such as genes that may be refractory to purification using biochemical means. These screens may have a pooled or arrayed format that allows researchers to monitor changes in gene expression. They can also be used to assess and validate the biological activity of molecules against a target, thus helping in hit identification.
Applications in Drug Discovery and Research
Cell-based assays are indispensable tools in drug discovery and biomedical research. The key challenge in drug development is the high attrition rate due to toxicity, and scientists are focused on developing strategies capable of reducing this rate. One such strategy is to determine cytotoxicity and safety risks early in the drug development pipeline, and cell-based assays can play a key role.
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In basic life science research, cell-based assays can help to understand the mechanisms underlying various biochemical processes in cells, irrespective of the physiological or pathological states.
In the pharmaceutical industry, these assays help in various stages of drug discovery and development. In the drug discovery stage, they can help to screen and validate targets. These high-throughput techniques can assist in screening libraries of compounds to identify hits against a biological target. Thereafter, these assays can help optimize lead during drug development. These assays quantify cytotoxicity and biological activity associated with the hit compounds. Lead optimization helps to eliminate the risks of adverse effects and maximize the potency of the identified hits. In addition to hit identification and lead optimization, cell-based assays are used to study the mechanism of action of the lead candidates.
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