A team led by Mojica identifies an enzyme with promising properties for gene editing
A team from the Molecular Microbiology Department at the University of Alicante (UA), led by Francisco Mojica, has identified a new enzyme with promising properties for CRISPR-Cas gene-editing tools. Mojica, an honorary member of the Official College of Biologists of the Valencian Community since 2018, is primarily known for his contributions since 1993 describing CRISPR repeat sequences in archaea and their role in prokaryotic cell immunity mechanisms. His discoveries later crystallized into the development of CRISPR-Cas technology.
The term CRISP was, in fact, coined by Mojica himself as an acronym for Clustered Regularly Interspaced Short Palindromic Repeats in his doctoral thesis. His team was the first to point out in 2005 that such sequences could be related to bacterial immunity against certain viruses, a discovery that enabled genome editing using the CRISPR-Cas9 tools developed by Emmanuelle Charpentier, Jennifer Doudna, Feng Zhang, and other researchers. Mojica's work was recognized in 2016 with the Jaume I Prize for basic research and the BBVA Foundation Frontiers of Knowledge Award.
The new enzyme now identified by his team and named AlCas12a represents a significant advance in the fields of biotechnology, biomedicine, and agri-food, reports the University of Alicante press office. Derived from a metagenome (genetic material) obtained from wastewater, AlCas12a is 20% smaller than currently available variants, a factor that facilitates its delivery to cells. Furthermore, it is highly flexible and has dual DNA-cutting activity, aspects that allow for targeting a greater number of sequences and increase the success rate of CRISPR techniques.
The development of this tool, led by Francis Mojica, Professor of Microbiology at the University of Alicante, along with researchers Ignacio Baquedano, Javier Espinosa, Noemí Marco, and Riccardo Rosselli, “represents a step forward in high-precision gene editing in plants and animals, in the rapid detection of pathogens, in the development of virus-resistant bacteria, and in the production of next-generation antibacterial agents as an alternative to traditional antibiotics,” they explain.
CRISPR-Cas technologies have revolutionized science by allowing for precise, rapid, and cost-effective gene modification. Thanks to these technologies, scientists worldwide can “cut” and “paste” DNA to eliminate mutations, introduce genetic enhancements, or develop innovative therapies. In this regard, “the AlCas12a enzyme, being so compact, versatile, and possessing new functions, is an advance over the editing techniques we already know,” adds Mojica.
Characteristics
One of the transformative features of AlCas12a is its dual DNA-cutting capacity: cis and trans. The cis-cutting mechanism allows for targeted action, like "molecular scissors" programmed to recognize a specific sequence in the genome, cutting a fragment of DNA at a precise point to modify or replace it.
Secondly, the trans-cutting mechanism can degrade single-stranded genetic material in a non-specific manner. "This function helps detect the presence of viruses or bacteria and paves the way for developing faster and more sensitive diagnostic tests," notes the UA microbiologist.
Furthermore, researchers have discovered that AlCas12a can act even without RNA guidance, something unusual in this type of enzyme, allowing it to attack the invading genome without needing to recognize a specific sequence. "It acts as a comprehensive defense system, providing bacteria with both innate and adaptive immunity," explains Mojica.
In laboratory tests, AlCas12a has successfully edited genes with 94% accuracy and protected bacteria from various types of viruses. Experiments have also confirmed that the enzyme maintains its activity across a wide temperature range, from 20 to 45 °C, making it compatible with a variety of organisms, from bacteria to plants and animals.
“All these characteristics, along with its compact size, make AlCas12a a revolutionary tool for use in gene therapies, biomedical research, and agricultural applications,” emphasizes the professor from the University of Alicante (UA).
The UA's Office for the Transfer of Research Results (OTRI) has included the discovery of AlCas12a in its technology offerings for companies interested in acquiring a patent license for its commercial exploitation.