The Promise of Genome Editing Tools to Advance Environmental Health Research Proceedings of a Workshop—in Brief (2018) / Chapter Skim
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The Promise of Genome Editing Tools to Advance Environmental Health Research: Proceedings of a Workshop - in Brief
The Promise of Genome Editing Tools to Advance Environmental Health Research: Proceedings of a Workshop - in Brief
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Standing Committee on Emerging Science for Environmental Health Decisions held a 2-day workshop to explore what role genome and epigenome editing tools could play in advancing environmental health research and decision-making. The workshop, sponsored by the National Institute of Environmental Health Sciences (NIEHS)
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Genome editing tools allow researchers to remove that gene and see what happens. Zinc finger proteins, TAL effectors, CRISPR/Cas9, and other tools can also be epigenome editors.
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Zinc fingers and CRISPR/Cas9 can be engineered to clinical grade nuclease specificity. However, a critical question for using genome editing tools in the clinic, as well as for research, is how likely can the tools alter segments of DNA that are not the intended target for editing, i.e., off-target effects.
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Adding to the appeal of genome editing tools is their promise for use in untargeted toxicology and environmental health studies that can shed light on previously unsuspected linkages between environmental exposures 6 Xia, P., X Zhang, Y
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The fact that genome editing tools are available "off the shelf" and can be purchased at a reasonable cost adds significantly to their appeal, observed Norbert Kaminski of Michigan State University. EMERGING USES OF GENOME EDITING TOOLS The projects under way that provide insights into how genome editing tools can aid environmental health research include work by David H
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Hahn's investigations using genome editing to flesh out the understanding of molecular mechanisms of chemical sensitivity associated with developmental toxicity involve work with the AHR using fish models. "Many fish are exposed to high concentrations of chemicals in the environment, so they can serve as good models for population-level impacts," he said.
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After mapping these rats' genomes, the group identified a candidate gene, C17h6orf52, associated with metabolic syndrome. Working with the Gene Editing Rat Resource Center, they generated two mutant lines with deletions in the gene using CRISPR/Cas9.
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Woychik said that genome editing tools can be used to complete studies that take much longer and are much more expensive with the traditional homologous recombination techniques. This includes quickly creating synthetic genomes to study the function of single genes, as well as to produce and study single nucleotide variations within promoter, coding, and non-coding regions.
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Houck said he is very interested in studying mixtures, but it is a huge combinatorial problem. However, he said it would be possible to set up potential models where scientists expect to see synergistic effects and then use gene editing tools to validate the ideas.
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He said that he believes these kinds of studies "are really valuable, in particular, for the kind of work that we're doing with so many unknown chemicals." Assuming that risk assessment continues to integrate high throughput testing, more proof-of-concept and pilot studies with well-characterized chemicals will help environmental risk assessors integrate functional genomics, including genome editing, Houck said. He would like to see the development of assay technologies that facilitate the expansion of functional endpoints beyond cell viability, for example, cell line engineering of pathway reporters that drive lethality, sorting on reporter gene expression, and single cell RNA sequencing could all generate useful data.
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Consumer Product Safety Commission observed that genome editing tools' potential to shed light on the drivers of individual susceptibility in response to chemical exposures might in time allow scientists to identify susceptible populations and perhaps even help them to resist the development of disease. Similarly, Linda Wennerberg of NASA said that in addition to identifying potential harms that can result from environmental exposures, genome editing tools may bring to light details about protective measures, such as ones involving nutrition, that can be taken to make people less vulnerable.
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The review comments and draft manuscript remain confidential to protect the integrity of the process. Organizing Committee on Emerging Genome Editing Tools to Advance Environmental Health Research: From Cells to Populations: A Workshop: Lesa Aylward, Summit Toxicology; David Gerhold, National Center for Advancing Translational Sciences; Norbert Kaminski, Michigan State University, Shruthi Mahalingaiah, Boston University School of Medicine; Gary Miller, Emory University, Reza Rasoulpour, Dow AgroSciences, Treye Thomas, U.S.
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