Simulation of liposomal nanostructures formed with ionizable cationic lipids loaded with mRNA using the DPD method

mRNA is a biomolecule that receives the genetic message from DNA and carries it to the ribosome for protein synthesis. External mRNA can be transferred to the cell to synthesize the protein of a gene it does not possess. With the development of biotechnology, delivering precisely structured mRNA into the cell has become an important research topic. Since mRNA carries protein synthesis codes, it holds great potential in genetic therapies and vaccine development, but its sensitive structure makes direct delivery to the cell challenging. Nanotechnology shows promise in overcoming this problem, as nanostructures have high potential for transporting mRNA into the cell. These nanostructures, which can be formed from various materials, offer advantages such as biocompatibility and increased bioavailability. Lipid nanostructures are particularly promising carrier systems for the safe and effective transport of mRNA, given that lipids are biomolecules also found in the cell membrane. Lipid nanostructures with biosafety, long circulation time, and modifiable properties attract attention as gene and drug carrier systems. Ionizable cationic lipids, in particular, are seen as safer and more effective candidates among liposomes due to their pH sensitivity, ability to stabilize negatively charged nucleic acids with their positive charges, integration into the cell membrane, and ability to escape the immune system. Molecular Dynamics (MD) simulations study intermolecular and intramolecular interactions using computer technologies. MD simulations can produce results compatible with experimental data, providing researchers with cost and time savings and vii a better understanding of molecular-level interactions. Dissipative Particle Dynamics (DPD), used for simulating complex biological systems, can perform efficient simulations on high time scales and in large systems, making it ideal for studying interactions between ionizable cationic lipids and precisely structured mRNA. This study aims to perform simulations using the DPD method to understand the behavior of ionizable cationic lipids used in mRNA-drug carrier systems and to examine intermolecular and intramolecular interactions in detail. By using the DPD method to examine nanostructures formed with ionizable cationic lipids in the transport of mRNA into the cell, this study aims to contribute to the knowledge in this field and help determine new and effective strategies in developing mRNA transport systems. In this thesis, the Dissipative Particle Dynamics method will be used to examine in detail the mRNA transport mechanism and the intermolecular interactions of the nanostructure formed with ionizable cationic lipids.