The ability to precisely modify genomes has profoundly changed biological research and opened new possibilities in biotechnology and medicine. While CRISPR-based genome editing tools have enabled programmable changes to DNA, a universal strategy for efficient and precise gene targeting and insertion across different organisms and cell types is still lacking. This limitation represents a major bottleneck for many applications, from basic research to gene therapies.
Transposons are natural gene transfer vehicles found in virtually all forms of life. Through their distinctive ability to mobilize DNA within and between genomes, they have played a central role in shaping genome architecture, regulation, and evolution. These same properties make transposons attractive candidates as broadly applicable genome engineering tools. However, despite their ubiquity and biological importance, the molecular mechanisms underlying many transposon systems remain poorly understood, and their technological potential for site-specific DNA manipulation is only beginning to be explored.
The overall goal of the BROADCAST project is to advance our mechanistic knowledge of recently identified RNA-guided DNA transposons in order to understand their biology and guide their repurposing as next-generation genetic technologies. The project focuses on three main directions: first, revealing how CRISPR-associated transposons (CASTs) achieve targeted DNA cut-and-paste reactions (Objective 1); second, studying newly discovered transposon-encoded proteins that act as RNA-guided DNA targeting enzymes, with the ultimate goal of supporting their application as versatile genome editors (Objective 2); and third, using insights into CASTs to develop programmable DNA insertion tools (Objective 3).
By combining fundamental biological research with early translational efforts, BROADCAST aims to advance the molecular understanding of transposition while laying the groundwork for novel genome editing approaches. In the long term, the project’s outcomes may expand the precision and wide applicability of strategies for genetic manipulation, with potential relevance to genome research, biotechnology, and biomedical applications.
