The Molecular Microbiology research group at the University of Alicante (UA) has identified a new enzyme with promising properties for CRISPR-Cas gene editing tools. Named AlCas12a, this protein represents a significant breakthrough in the fields of biotechnology, biomedicine, and the agri-food industry.
Identified within a metagenome (genetic material) sourced from wastewater, AlCas12a is 20% smaller than existing commercial variants, a characteristic that facilitates more efficient cellular delivery. Moreover, the enzyme exhibits remarkable flexibility and possesses dual DNA cleavage activity. These attributes enable the targeting of a broader range of sequences, thereby enhancing the overall efficacy of CRISPR-based techniques.
The development of this tool was led by Francis Mojica, Professor of Microbiology at the UA, along with researchers Ignacio Baquedano, Javier Espinosa, Noemí Marco, and Riccardo Rosselli. They explain that this represents a step forward in high-precision gene editing in plants and animals, rapid pathogen detection, the development of virus-resistant bacteria, or the production of next-generation antibacterial agents as an alternative to traditional antibiotics.
CRISPR-Cas technologies have revolutionised science by allowing genes to be modified precisely, quickly and affordably. These tools enable scientists worldwide to ‘cut and paste’ DNA to remove mutations, introduce genetic improvements or develop innovative therapies. In this regard, Professor Mojica adds that the AlCas12a enzyme, being so compact, versatile and having new functions, is a breakthrough for existing editing techniques.
Features
One of the transformative features of AlCas12a is its dual DNA-cutting capacity: cis and trans. The former acts in a targeted manner, like ‘molecular scissors’ programmed to recognise a specific genome sequence; that is, cutting a DNA fragment at an exact point to modify or replace it.
Secondly, trans-cleavage can degrade single-stranded genetic material non-specifically. This function helps detect the presence of viruses or bacteria and paves the way for faster and more sensitive diagnostic tests, as noted by the UA Professor.
Furthermore, the researchers discovered that AlCas12a can function even without an RNA guide, which is unusual for this type of enzyme. This allows it to attack the invading genome without needing to recognise a specific sequence. The ezyme behaves as a comprehensive defence system, providing bacteria with both innate and acquired immunity, the microbilogist explained.
In laboratory tests, AlCas12a achieved 94% accuracy in gene editing and protected bacteria from various types of viruses. Experiments also confirmed that the enzyme remains active across a wide temperature range, between 20 and 45 °C, making it compatible with a variety of organisms, from bacteria to plants and animals.
According to Mojica, these features, combined with its compact size, make AlCas12a a revolution for use in gene therapies, biomedical research and agricultural applications.