Controlling Protein Expression by Delivery of RNA Therapeutics Using Lipid Nanoparticles

Dysregulated protein expression is the basis for a wide variety of diseases ranging from cancer to metabolic diseases. The ability to normalize protein levels, by introducing either messenger RNA (mRNA) or small interfering (si)RNA to the cytoplasm of target cells to address loss of a vital protein or overexpression of a disease-causing protein, respectively, highlights the significant therapeutic potential of RNA. However, while intracellular RNA delivery can be easily achieved in vitro, in vivo application represents a significant challenge, the main hurdles being cytoplasmic delivery across the membrane of target cells while maintaining the stability in circulation. Lipid nanoparticles (LNPs) represent a highly advanced drug delivery system, which has proven to be effective for the in vivo delivery of nucleic acid drugs. In this chapter we will be describing LNP-based delivery of therapeutic RNA drugs (siRNA and mRNA) in the context of preclinical studies as well as those already in clinic.