Use of Genetic Manipulation for Evaluating and Understanding Adverse Outcome Pathways

Innovations in biology have brought forth a new era of genetic manipulation ranging from the creation of molecular scissors for targeted single-nucleotide alterations, to a simultaneous inactivation of 62 genes in pig embryos to “humanize” transplant tissue. Genetic engineering advances allow for novel testing paradigms to understand chemical interactions and information flow in biological systems. Emerging platforms may provide mechanistic knowledge of chemical stressor interactions in biological systems to facilitate the development of alternative testing methods, as well as prioritize higher tier toxicity testing for risk assessment. This chapter will discuss recent advances in genetic manipulation and describe how these techniques improve our understanding of toxicity across multiple biological scales. These efforts will ultimately aid in validation of Adverse Outcome Pathway (AOP) key event relationships for ecological risk assessment.