These days, it’s difficult to ignore the buzz around Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9, a revolutionary tool for making targeted genomic perturbations that has sent shock waves throughout translational biology research. In the field of toxicology, CRISPR allows for targeted investigations into the mechanisms underlying toxicity, disease susceptibility, and the interactions between genes, exposures, and adverse biological outcomes. Many toxicologists (including myself) have likely considered adapting CRISPR into their own research projects, but the learning curve for this molecular biology tool can seem daunting.
The Workshop Session “Advances in CRISPR-Based Molecular and Computational Methods for Assessing Mechanistic Underpinnings of Toxicity and Gene-Environment Interactions” during the 2022 SOT Annual Meeting discussed the current state of CRISPR research, focusing on the adaptability of this technology to toxicology studies. My own research focuses on in vivo exposure studies and bioinformatics, so I was particularly interested in the session’s third speaker, Dr. Robyn Tanguay, who talked about her research combining a zebrafish exposure model, toxicogenomic measures of phenotype, and targeted follow-up using targeted CRISPR-cas9 gene editing to test involvement of candidate genes in toxicity.
In her talk, Dr. Tanguay emphasized the utility of CRISPR-cas9 in extending associations from bioinformatics approaches into testable gene-environment mechanisms. In particular, she showed data where gene editing was used to establish a causal relationship between specific aryl hydrocarbon receptors and polycyclic aromatic hydrocarbon toxicity. This highlights how CRISPR methods can help toxicologists “lean into the complexity” and validate toxicological findings, particularly those identified in experiments using ’omics technologies and bioinformatics methods. This type of translation from large-scale association study to empirical target gene experiment is critical as the field of toxicology continues to generate larger and larger datasets.
The other two talks, presented by Drs. Chris Vulpe and Katherine Shortt, further demonstrated the adaptability of CRISPR-cas9 to additional experimental contexts. Dr. Vulpe discussed the recent use of genome-wide CRISPR screening as a systematic approach to clear up experimental “muck” and investigate the relationship between human genes and different toxicants, including formaldehyde and dieldrin. His talk focused on the utility of CRISPR-based functional profiling as a tool to create ranked lists of genes that respond to toxicants. Meanwhile, Dr. Shortt described the specific use of this type of genome-wide CRISPR-cas9 screen in evaluating the potential role for different human genes in acetaminophen (APAP)–induced liver injury. Using an in vitro HuH7 hepatocellular carcinoma cell model, Dr. Shortt showed how CRISPR can be used to identify candidate genes involved in drug toxicity, providing new avenues to assess gene “druggability.”
Though intimidating for inexperienced users like myself, I walked out of this session optimistic about the future of CRISPR methods in toxicology research. All three presentations highlighted the efficiency and flexibility of this technology, demonstrating how gene editing methods can be incorporated into a wide variety of experimental paradigms, including in vitro screening assays and in vivo gene-environment interaction models. Furthermore, CRISPR-based experiments can help validate genetic hits identified in ’omics studies, allowing for phenotypic interpretation of predictive modeling results.
As I left the session, it was clear that the buzz is real—CRISPR-cas9 is here to stay.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.
On-demand recordings of all Featured and Scientific Sessions delivered during the 2022 SOT Annual Meeting and ToxExpo will be available to meeting registrants in the SOT Event App and Online Planner after their conclusion, through July 31, 2022.
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