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<\/p>\nThe scientific team led by Miguel \u00c1ngel Moreno Mateos, researcher at the Andalusian Center for Developmental Biology (CABD), a joint center of the Spanish National Research Council (CSIC), the Pablo de Olavide University (UPO) and the Regional Government of Andalusia, has managed to optimize different CRISPR-Cas systems in vivo using zebrafish as a model and that, unlike the most widely used and well-known CRISPR-Cas technology that cuts DNA, these systems mediate RNA editing. This technology could have great utility in future biomedical therapies based on RNA manipulation.<\/p>\n
On the one hand, the researchers have optimized the use of chemically modified RNA guides (gRNA), which together with the messenger RNA (mRNA) of RfxCas13d allows the effective elimination of RNAs for a longer time that will help extend the capacity of the tool over time and its potential utility in effective and transient RNA elimination therapies. In addition, this work has optimized the elimination of RNAs in the nucleus by using new nuclear localization signals fused to Cas13d, which can potentially contribute to using this technology for treatments involving the elimination of RNAs that are only found in the cell nucleus, such as certain non-coding RNAs or microRNAs for which more and more functions are known than originally thought in different contexts such as embryonic development or cancer.<\/p>\n
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This image shows 2-day-old zebrafish larvae in which rx3 messenger RNA has been deleted with CRISPR-RfxCas13d. This gene is involved in eye formation, so from left to right you can see a major defect until complete removal of both eyes.<\/em><\/p>\n Since the use of a large number of chemically synthesized guides is costly, the research group has developed, as an alternative, a simple protocol to perform an analysis with in vitro synthesized gRNAs and rule out possible toxicity before injection: \u201cThis technique provides a reliable and specific option for laboratories with a low budget,\u201d says one of the researchers, Luis Hern\u00e1ndez-Huertas, who together with Daniel Nah\u00f3n-Cano and Ismael Moreno S\u00e1nchez has led the project.<\/p>\n The CRISPR-RfxCas13d RNA elimination system can present a non-specific activity after specifically eliminating its target called ‘collateral activity’, therefore, the object of this research has also focused on the search for conditions in which the use of this tool transiently does not generate such collateral activity or, if there is any, it is minimal and does not generate a physiological impact on embryos. \u201cThese results confirm that the tool is not only efficient, but also safe in the vast majority of cases,\u201d says Daniel Nah\u00f3n-Cano, predoctoral researcher and co-author of this work. Even so, the researchers have fine-tuned the conditions to eliminate RNAs effectively and specifically with two other alternative CRISPR systems that generate zero or very low collateral activity, namely CRISPR-Cas7-11 and CRISPR-DjCas13d. \u201cThese new optimizations in the CRISPR-RfxCas13d system and the fine-tuning of two other CRISPR-Cas systems for RNA elimination contribute to expand the molecular toolbox for RNA elimination and provide more options available to the scientific community,\u201d says Ismael Moreno-S\u00e1nchez, postdoctoral researcher and one of the first authors of the work.<\/p>\n In summary, the knowledge acquired in this work contributes to improving transient RNA degradation systems and facilitates the access of this technology to future therapies in biomedicine. In addition, the development of more CRISPR-Cas RNA editing systems will allow multiplexing experiments, i.e., against several targets at the same time, thus circumventing problems related to gene redundancy or modeling developmental diseases caused by the lack of function of several RNAs at the same time.<\/p>\n This research has also involved the collaboration of scientific groups from the Stowers Institute, the Instituto de Neurociencias de Alicante and the American company Synthego Corporation, among others.<\/p>\n Reference:<\/p>\n Moreno-S\u00e1nchez, I., Hern\u00e1ndez-Huertas, L., Nah\u00f3n-Cano, D.\u00a0et al.<\/i>\u00a0<\/span>Enhanced RNA-targeting CRISPR-Cas technology in zebrafish.\u00a0Nat Commun<\/span><\/i>\u00a016<\/b>, 2591 (2025). https:\/\/doi.org\/10.1038\/s41467-025-57792-9<\/span><\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":" Scientific advancesOptimized version of CRISPR technology developed with potential for future biomedical therapies Research published in the journal ‘Nature Communications’ contributes to improving the molecular toolbox for RNA knockout, providing […]<\/p>\n","protected":false},"author":2999,"featured_media":18735,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[184],"tags":[],"class_list":["post-18740","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-scientific-advances"],"_links":{"self":[{"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/posts\/18740","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/users\/2999"}],"replies":[{"embeddable":true,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/comments?post=18740"}],"version-history":[{"count":6,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/posts\/18740\/revisions"}],"predecessor-version":[{"id":26837,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/posts\/18740\/revisions\/26837"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/media\/18735"}],"wp:attachment":[{"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/media?parent=18740"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/categories?post=18740"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cabd.es\/en\/wp-json\/wp\/v2\/tags?post=18740"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}