Transgenesis: In the Drug Discovery Process, Including Target Identification and Target Validation

Transgenic targeting is the most dependable method for mouse transgenesis because it produces predictable transgene expression patterns. This method is ideal for large-scale knock-in target assessments. Furthermore, transgenic targeting is the preferred method for getting around the restrictions since it is a powerful cellular delivery strategy. The chapter introduces the concept of target validation and underscores its significance in evaluating a target’s potential for therapeutic benefits. The focus is on improving the drug development process through early target validation. Target validation, a critical initial step taking few months, involves proving that altering the target in animals and cell cultures significantly improves the disease phenotype. Target validation in transgenic animals is explored in detail, emphasizing the necessity of clearly defining a model’s objectives for appropriate creation, evaluation, and application. The difficulties of accurately simulating human genetic abnormalities in transgenic animals are discussed despite the possibilities offered by genome editing. The importance of validity in assessing animal models is reiterated, advocating continuous debate and improvement. The translational method is emphasized for differentiating between target validations in humans and qualifying in animals. Face and construct validity in animal models are explained, with the latter deemed more crucial. The challenges of simulating human genetic disorders in transgenic animals are acknowledged, with the recommendation to use diverse models to improve predictive validity.