There are several methods used to deliver RNA molecules into cells: 

  • Mechanical methods, such as electroporation and sonoporation, create temporary pores in cell membranes that enable RNA entry. 
  • Chemical methods, such as lipofectamine and PEI, rely on the formation of complexes with cationic lipids or polymers that favor interactions with cell membranes and RNA entry. 
  • Viral vectors, such as adeno-associated viruses (AAV), carry RNA molecules and deliver them to target cells. 
  • Non-viral delivery systems, such as liposomes, polymeric nanoparticles, and lipid nanoparticles (LNPs), encapsulate, protect, and deliver mRNA to the target cells. The specific properties, safety, and efficacy of transfection depend on the composition of the delivery systems. Among them, LNPs are the only mRNA non-viral delivery systems that have reached the clinic. 

Mechanical and chemical methods typically harm cells and show toxicity, while they cannot be applied in an in vivo setting. Viral delivery, while effective in delivering the genetic material to the nucleus of the cells and helping integrate the DNA into the genome of the host, still poses safety concerns. In this regard, nanoparticles can definitively provide a solution towards the clinical approval of more gene therapies.