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Research Project: Validate Causative Mutations in Agriculturally-Important Vertebrates

Location: Plant Genetics Research

Title: Response to cook et al. re: novel off-targeting events identified after genome wide analysis of CRISPR-Cas edited pig

Author
item Redel, Bethany
item LEE, KIHO - University Of Missouri

Submitted to: The CRISPR Journal
Publication Type: Other
Publication Acceptance Date: 1/12/2025
Publication Date: 4/17/2025
Citation: Redel, B.K., Lee, K. 2025. Response to cook et al. re: novel off-targeting events identified after genome wide analysis of CRISPR-Cas edited pig. The CRISPR Journal. 8(2): 77-78. https://doi.org/10.1089/crispr.2025.0003.
DOI: https://doi.org/10.1089/crispr.2025.0003

Interpretive Summary: Not required

Technical Abstract: A group of geneticists and data scientists from the FDA are writing a commentary addressing areas for improvement to a previously published manuscript, "Novel Off-Targeting Events Identified after Genome Wide Analysis of CRISPR-Cas Edited Pigs" in the June issue of The CRISPR Journal. This manuscript is a response to their commentary and will be published along side their commentary in an upcoming issue of The CRISPR Journal. Their correspondence identified three different areas for improvement to our original manuscript. The improvements are three fold: 1) increase the number of potential off-target genomic sites analyzed by downloading the off-line version of Cas-OFFinder, 2) identify possible structural variants due to genome editing, and 3) utilize a different bioinformatics tool for analyzing somatic variants as a means for identifying mosaic variants. While we acknowledge the technical aspects that were brought up by the correspondence, the identification of every potential off-targeting event was beyond the scope of this study. The main purpose of our study was to identify off-targeting events that were blended in genomic alterations against the reference genome. Interest from federal agencies, such as FDA, should encourage other researchers to investigate more effective ways to identify off-targeting events. It would be great for academia and regulatory agencies to work together to identify the best methods for identifying off-target events in a challenging species, such as the pig.