A cold-adapted Cas9 nuclease from the deep ocean

Olaso-Llorca, A.; Colizzi, F.; Mingarro, G.; Sanchez, P.; Sanchez-Bolanos, C.; Molina, C. A.; Martinez-Cazorla, A.; Serrano-Duran, R.; Urbaitis, T.; Rodrigo Melero, N.; Bosch, A.; Magallon-Mosella, M.; Margitfalvi, M.; Stitilyte, M.; Carolis, C.; Romero-Moya, D.; Giorgetti, A.; Velazquez-Mudarra, A.; Rajkovskii, D.; Del Cano-Ochoa, F.; Lopez-Farfan, D.; Gomez, J.; Ferrandez-Roldan, A.; Ramon-Maiques, S.; Gomez Diaz, E.; Canestro, C.; Duarte, C. M.; Gasol, J. M.; Mojica, F. J. M.; Sanchez-Amat, A.; Moreno-Mateos, M. A.; Gasiunas, G.; Acinas, S. G.; Ceron, J.

doi:10.64898/2026.10.14.759226

Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.10.14.759226

A cold-adapted Cas9 nuclease from the deep ocean

View original source ↗Export metadata ↓

Abstract

The abundance of CRISPR systems in bacteria and archaea fuels the search for Cas nucleases that perform where established enzymes fail. Deep Ocean 1 Cas9 (DO1Cas9) is to our knowledge the first Cas9 nuclease characterized from the deep ocean, recovered from a metagenomic sample at 1,500 m depth in the Atlantic Ocean. DO1Cas9 shows cold-adapted structural flexibility, thermal susceptibility, salt-dependent stability, higher specificity than SpCas9 and cleaves double-stranded DNA efficiently under cold conditions where mesophilic SpCas9 retains only residual activity. DO1Cas9 edits genomes in diverse organisms such as Caenorhabditis elegans, zebrafish, the marine tunicate Oikopleura dioica, and the malaria parasite Plasmodium falciparum. In the marine bacterium Marinomonas mediterranea, DO1Cas9 programmed against an invading phage reduced plaquing efficiency about 10-fold more than SpCas9. These results expand the CRISPR-Cas9 toolbox with a nuclease for cold-chain editing and marine biotechnology.

Explore related subjects

genetics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Olaso-Llorca, A., Colizzi, F., Mingarro, G., Sanchez, P., Sanchez-Bolanos, C., Molina, C. A., Martinez-Cazorla, A., Serrano-Duran, R., Urbaitis, T., Rodrigo Melero, N., Bosch, A., Magallon-Mosella, M., Margitfalvi, M., Stitilyte, M., Carolis, C., Romero-Moya, D., Giorgetti, A., Velazquez-Mudarra, A., Rajkovskii, D., Del Cano-Ochoa, F., Lopez-Farfan, D., Gomez, J., Ferrandez-Roldan, A., Ramon-Maiques, S., Gomez Diaz, E., Canestro, C., Duarte, C. M., Gasol, J. M., Mojica, F. J. M., Sanchez-Amat, A., Moreno-Mateos, M. A., Gasiunas, G., Acinas, S. G., Ceron, J.. 2026-10-16. A cold-adapted Cas9 nuclease from the deep ocean. https://doi.org/10.64898/2026.10.14.759226

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

STING deficiency extends median lifespan and mitigates age-related liver pathology in mice

The cGAS-STING pathway is a major driver of chronic inflammation. While acute STING inhibition can reduce neuroinflammation and tissue damage, its long-term impact on longevity remains unknown. Here, we demonstrate that genetic deletion of STING extends median lifespan in mice. This survival benefit is accompanied by a marked resistance to age-related hepatic decline. Our findings demonstrate that targeting STING is a promising therapeutic target to extend healthy lifespan.

genetics↗

bioRxiv2026

Comparison of the performance of sporophytes derived from narrow and wide genetic crosses between strains of the cultivated kelp Saccharina latissima

Seaweed mariculture allows sustainable production of large quantities of biomass for multiple downstream applications but the genotypes cultivated by this industry need to be improved to increase efficiency and cost-effectiveness. It is important that the genetic improvement of cultivated strains does not lead to the introduction of foreign genetic material into wild seaweed populations, which are already under threat from global heating. To circumvent this problem, efforts are being made to develop breeding approaches based on the use of locally-resourced genetic material. The aim of this study was to evaluate the potential effectiveness of this 'local' breeding strategy compared to a classical breeding approach based on wide genetic crosses. Analyses of growth rates and cell wall composition of F1 hybrids derived from either intra- or inter-population crosses between Saccharina latissima strains from two localities, southern Brittany, France and the Faroe Islands, did not identify any clear advantage of inter- compared to intra-population crosses. Breeding based on locally-resourced strains would therefore appear to be a valid approach for current strain selection programs. The study also established a large collection of gametophyte strains from multiple sites for future breeding programs and showed that these strains retained the capacity to become fertile after more than ten years in culture.

genetics↗

bioRxiv2026

Sample overlap in genome-wide association meta-analysis: practical comparisons across significance thresholds

Meta-analysis is widely used in genome-wide association studies (GWAS) to combine evidence across studies without requiring individual-level data. However, as both the number of studies included in meta-analyses and their sample sizes continue to grow, the same participant may be included in more than one study. Such sample overlap induces dependence across studies and violates the independence assumptions underlying standard meta-analysis methods. HostSeq is a Canadian initiative in which 15 clinical and epidemiological studies were assembled with DNA samples from approximately 10,000 Canadians infected by the SARS-CoV-2 virus. We observed duplicate samples across different participating studies. This observation raises an important practical question: what is the impact of sample overlap on association results, and when should such overlap be a concern? Motivated by this real problem, we sought to compare five meta-analysis methods and evaluate their performance against a reference mega-analysis in which the true sample overlap is known. We show that when the degree of sample overlap is relatively small, its impact on association results is minimal, even at the genome-wide significance threshold of = 5*10 -8 . We demonstrate these findings through extensive simulation studies and an application to overlapping cohorts within HostSeq.

genetics↗