A research team led by Prof. Frank Buchholz at the Medical Faculty Carl Gustav Carus of the Technische Universität Dresden has achieved a major breakthrough in genome editing technology. They have developed a state-of-the-art method that combines the capabilities of designer recombinases with programmable DNA-binding domains to create precise and adaptable genome editing tools.
Traditional genome editing methods have had limited potential to achieve the highest precision. Prof. Buchholz’s team has overcome this barrier by creating what many have been searching for: a zinc finger-templated recombinase. This innovative approach involves the integration of a zinc finger DNA-binding domain into specially designed recombinases. These enzymes remain inactive until the DNA-binding domain attacks its target site alongside the recombinase-binding region.
The significance of this achievement lies in the combination of two key strengths: the simple target accuracy of programmable nucleases and the precise DNA editing capabilities of recombinases. This breakthrough overcomes existing limitations in genome editing techniques and holds promise for therapeutic gene editing and various biomedical applications.
Prof. Buchholz expresses his enthusiasm, stating, „This breakthrough represents a harmonization of existing genome editing tools, allowing us to develop precision enzymes that are independent of natural DNA repair mechanisms. This marks a significant step toward a safer and more adaptable approach to correcting genetic mutations, offering tremendous benefits for numerous patients.“
This groundbreaking work opens new horizons in genome surgery and promises a safer and more precise approach to treating genetic disorders. The impact of this breakthrough is far-reaching and has the potential to change the landscape of medicine as we know it. Professor Esther Troost, Dean of the Faculty of Medicine at TU Dresden, emphasizes, „The Faculty of Medicine at TU Dresden is setting new standards for innovative medicine with groundbreaking genome editing tools under the leadership of Prof. Frank Buchholz.“ „The research team is breaking traditional boundaries and paving the way for specialized gene therapy applications.“
Building on these advancements, Seamless Therapeutics GmbH, a biotechnology company founded by the Buchholz laboratory, will translate these innovative findings into therapeutic applications. The company has signed an exclusive license agreement with TU Dresden for this novel technology, enabling Seamless to further expand its recombinase platform and change the paradigm of gene editing, developing a pipeline of disease-modifying product candidates for a wide range of indications.
Technische Universität Dresden
Mukhametzyanova, L., et al. (2024). Activation of Recombinases at Specific DNA Loci by Insertions of Zinc Finger Domains. Nature Biotechnology. doi.org/10.1038/s41587-023-02121-y