Johann Moritz Weck

Abstract The extrinsic activation of programmed cell death by FasR/CD95 is a promising minimally invasive strategy for cancer treatment. This can be leveraged using high-precision nanoscale therapeutics: Utilizing DNA origami for precise Fas ligand (FasL) presentation resulted in over 100 times more potent apoptosis induction in single cells. However, treating large, solid tumors poses challenges for DNA origami-based therapeutics, including drug distribution and altered cellular behavior.

Abstract Background: Cluster of differentiation 95 (CD95/Fas/Apo1) as part of the Tumor-necrosis factor (TNF) receptor family is a prototypic trigger of the extrinsic apoptotic pathway and its activation by the trimeric ligand CD95L is of high interest for anticancer therapy. However, CD95L, when presented in solution, exhibits a low efficiency to induce apoptosis signaling in human cells.

1 Introduction Life with all of its complex functions is based on the capacity of matter to self-organize. On the molecular level, proteins have the capability to spontaneously self-assemble into functional complexes. On larger scales, such as cells and organisms, self-assembly processes become less reliable, as a result of the inherent stochasticity of the self-assembling units and, in particular, the inefficiency of diffusion in targeting them to the sites of assembly.