B01

According to studies, 25% of patients in intensive care units develop Critical Illness Myopathy (CIM), which is not yet therapeutically treatable. Muscle inflammation is associated with the development of CIM in sepsis patients. There is also new evidence that inflammatory signaling pathways contribute to age-related impairments of muscle stem cells, also known as satellite cells (SCs). Upon injury, these cells are activated and finally differentiate into myotubes. Rudolph's team recently identified a Hox protein gene fragment, HoxM, which has the potential to reduce inflammatory and senescence signals, thereby improving the proliferative potential of activated stem cells in culture. Inhibition of the Hox genes by the newly discovered HoxM fragment could thus lead to a reduction of inflammation in sepsis induced CIM. For this purpose, multifunctional nanoparticles for the transport of mRNA encoding a therapeutic Hox gene fragment (HoxM) into muscle stem cells are being developed (Träger lab). The mRNA is encapsulated in cationic particles, which are then coated with anionic counter-polymers that can be functionalized with stealth polymers and/or target molecules. Different aspects such as cellular targeting and uptake of the nanoparticle, endosomal release and intercellular delivery of HoxM are investigated as well as the influence of the particles on muscle stem cell proliferation and the therapeutic effect of nanoparticle-mediated gene delivery.