We investigate new genome editing principles based on activating and guiding specific DNA repair processes after delivering into target cells gene editing tools consisting of programmable DNA-cleaving enzymes (nucleases or “nickases”) and exogenous DNA-repairing templates (donor DNA). We further study the genome editing outcomes (wanted and unwanted) resulting from using nucleases versus “nickases” and donor DNA substrates with different structures and topologies. This research seeks to achieve seamless and scarless chromosomal DNA editing for modelling or repairing genetic defects in pluripotent stem cells and tissue-specific stem/progenitor cells. Underpinning these investigations, we develop and integrate gene delivery and gene editing technologies grounded on recombinant viruses and programmable nucleases, e.g., adenoviral vectors and CRISPR systems, respectively.
Additional information on our research activities is available via the links:
PhD theses from lab alumni:
- Maarten Holkers "The roles of adenoviral vectors and donor DNA structures on genome editing" (2016) https://openaccess.leidenuniv.nl/handle/1887/37412.
- Ignazio Maggio (cum laude) "Adenoviral vectors as genome editing tools: repairing defective DMD alleles" (2016) https://openaccess.leidenuniv.nl/handle/1887/44288.
- LUMC Best Thesis Prize 2017 (Non-clinical).
- Greiner Award 2017 from the Netherlands Society of Gene and Cell Therapy for the best thesis in the field of Gene Therapy carried out at a Dutch University or Institute.
- Xiaoyu Chen "Determinants of genome editing outcomes: the impact of target and donor DNA structures" (2018) https://openaccess.leidenuniv.nl/handle/1887/62204.