ARTiCELL – Encapsulation and stabilization of genetic resources in artificial cell-like structures

• Applicants: Dr. Harriette Oldenhof; Professor Dr. Willem F. Wolkers
• Subject Area: Veterinary Medical Science
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 571356358

When dry preservation of gametes and/or genetic material were possible without loss of fertilizing potential, this can be implemented for securing genetic resources and would transform biobank facilities and the breeding industry. This would facilitate low-cost room temperature storage easing off-the-shelf availability and transport. Moreover, dry preservation methods for biologics can be implemented in underdeveloped countries, remote locations, and non-laboratory settings. Without taking protective measures, biomolecules in mammalian cells are subject to (irreversible) conformational changes during drying and specimens are prone to chemical degradation during storage, impairing their functions. Numerous attempts have been pursued to preserve cell viability and functionality in the dried state, mostly inspired by nature’s way to survive drying in a state of suspended animation referred to as anhydrobiosis. However, only limited successes have been reported in keeping ordinary mammalian cells viable after drying and subsequent rehydration. Attempts focused on the introduction of specific disaccharides (i.e., trehalose, sucrose), stress proteins, and membrane modification strategies, which play a role in acquiring desiccation tolerance in nature. However, the complex orchestrated cellular adaptation mechanisms of anhydrobiotic organisms are not likely to be mimicked in cells that are not naturally resistant to dehydration. Dried mammalian cells may retain their structure and specific functional properties. For example, dried sperm and somatic cells can be injected into (enucleated) oocytes for the production of offspring. However, under ambient conditions, biomolecules in dried cells are susceptible to rapid degradation during storage. Major factors impairing storage stability of biomolecular structures in a dried cellular environment are the presence of reactive molecules, environmental conditions, and inherent susceptibility for damage (e.g., degree of lipid saturation and chromatin condensation). We propose a different approach for long-term room temperature preservation of genetic resources; not focusing on recovering fully functional cells but by generating ‘artificial’ cell-like nuclei-containing structures. We plan to do this by (1) making ‘ghost cells’ from sperm to remove damaging reactive molecules normally present in the cells, while keeping organelles and cytoskeletal elements inside, and (2) by making demembranated sperm encapsulated in giant liposomes. In both cases, damaging reactive molecules in cells are removed, while protective molecules can be easily introduced.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Harald Sieme