Abstract
The cell membrane protects cells from damage by external factors. Nevertheless, cells can be damaged and therapy is needed. In such cases, the cell membrane forms a barrier. In particular, macromolecules such as DNA and proteins are effectively kept outside the cell, while inside the cell they can have a therapeutic effect. Cell-penetrating peptides (CPPs) are small peptides that can effectively cross the cell membrane and carry macromolecules. The activity of CPPs can be controlled by cutting them in half, rendering them non-functional, and then chemically gluing them back together to restore activity. This chemical bonding must take place in a biological environment without reacting with other chemical structures present. This form of chemistry is called bioorthogonal chemistry. In this PhD thesis, we developed a bioorthogonal chemistry in which part of the structure is also released after pasting. To this shed part, we attached a sensor specific to certain cell types to create cell-specific, activatable CPPs. In addition, we introduced the gene modification technique CRISPR/Cas9 into cells via these activatable CPPs and investigated how small structural modifications in the CPPs affect cell uptake.
