Shepherding precision gene editing with CRISPR-Cas9 variants and adenoviral vectors

Tasca, F. (2023)

Doctoral Thesis

The past two decades have seen the growing development and consequent vast application of next-generation genome editing tools in fundamental and applied research. Nowadays GE based on RNA-guided nucleases (e.g., engineered CRISPR-Cas9 nucleases) are the most common tools for targeted genetic modification. Nevertheless, these technologies are in need of increased efficiency and accuracy, especially looking forward to translation into diverse clinical applications. The work presented in this thesis focuses on improving the efficiency and accuracy of genome editing, particularly in cells with high therapeutic potential, such as induced pluripotent stem cells (iPSCs), by investigating the feasibility of using adenoviral vectors to test novel genome editing approaches and by exploring the possible applications of a scarless strategy.

• CRISPR-Cas9
• Genome editing
• Adenoviral vectors
• Gene editing
• Duchenne muscular dystrophy
• iPSCs
• Myoblasts

• All authors: Tasca, F.
• Supervisor: Hoeben, R.C.
• Co-supervisor: Gonçalves, M.A.F.V.
• Committee: Aartsma-Rus, A.M.; Goumans, M.J.T.H.; Geijsen, N.; Larcher, F.; Mikkelsen, J.G.; Mastrobattista, E.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2023-06-15