A multidisciplinary consortium led by the Institute of Marine Sciences of the Spanish National Research Council (ICM-CSIC), and in which Dr. Julián Cerón, leader of the C. elegans disease models group at IDIBELL, participates, has applied for the patent of two new gene-editing tools with unique characteristics compared to the most widely used canonical CRISPR-Cas9 system.
CRISPR and the need to explore to innovate
CRISPR-Cas9 technology is a gene-editing system that has revolutionized science this century, especially biomedical research, due to its ability to eliminate, edit or introduce new genes into organisms in a very precise way. In essence, this system is made up of a guide RNA capable of identifying and binding specifically to the DNA sequence to be edited, and a Cas9 protein that, like a genetic “scissors”, allows this sequence to be cut and modified.
The scissors that are most used in laboratories around the world, SpCas9, were discovered in the microorganism Streptococcus pyogenes, a pathogenic bacterium in humans that prefers medium temperatures. To expand the toolbox with gene-editing systems that work at other temperatures or edit other types of genes, it is necessary to explore different environments in search of the microorganisms that carry them.
Asterix and Obelix, the new genetic scissors
This is precisely what was achieved with the Malaspina oceanographic expedition in 2010, which made it possible to obtain a robust microbial genetic database of the ocean floor with which to design two new gene-editing tools, DO1 and DO2 (DO from “Deep Ocean”). As Silvia G. Acinas, microbiologist at the ICM-CSIC and coordinator of the genetic analysis of the samples from the expedition that led the research, points out, “Our two Cas9, which come from the deep ocean, have different biophysical properties that can facilitate new applications. For example, one is able to cut at low temperatures very precisely.”
Dr. Julián Cerón, co-inventor of both tools, adds that they are very efficient and have unique and differential characteristics compared to conventional CRISPR-Cas9. “In the laboratory we call them Asterix and Obelix because they are very efficient in their activity of cutting DNA,” he says, referring to the famous comic book characters who fought the Romans. “In addition, they work well at colder temperatures than canonical SpCas9, expanding the range of conditions under which these tools can work in laboratories,” reveals the expert. Due to the high transfer potential of this project, they have received the CERCA GINJOL Patents Fund and BlueNetVal 2025 grants to bring these tools to the market.
“Asterix is smaller than SpCas9 and therefore more manageable in biotechnology, while Obelix, larger, has a PAM recognition sequence that identifies the gene to be cut and is equivalent to that of SpCas9. Thanks to this, we can use our Cas9 as an alternative to edit in the same regions of DNA that SpCas9 uses,” explains Dr. Cerón.
However, in this sense, the expert stresses that “it is not a question of replacing SpCas9, which will continue to be useful, but of expanding the current gene-editing toolbox with new variants like ours.” To continue knowing their full potential, they are now studying their off-target rates, since the new Cas9 from the deep ocean seem to be more specific than SpCas9.
The special support of Francis Mojica
Scientific collaboration played a fundamental role from the very beginning of the project, which has also involved one of the fathers of CRISPR systems. It is precisely with Francis Mojica, the person who coined the term CRISPR in 2001 and one of the first to identify this system, with whom the researchers of this project are writing an article where they will share these findings with the international scientific community.
Piece adapted from the original report by Ana Lozano, carried out as part of the CSIC-BBVA Foundation Grant Program for Scientific Communication, Call 2023.
The Bellvitge Biomedical Research Institute (IDIBELL) is a research center established in 2004 specialized in cancer, neuroscience, translational medicine, and regenerative medicine. It counts on a team of more than 1.500 professionals who, from 73 research groups, publish more than 1.400 scientific articles per year. IDIBELL is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona, and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).