Targeted lipid nanoparticles for RNA therapeutics and immunomodulation in leukocytes.

Abstract Abnormalities in leukocytes' function are associated with many immune related disorders, such as cancer, autoimmunity and susceptibility to infectious diseases. Recent developments in Genome-wide-association-studies give rise to new opportunities for novel therapeutics. RNA-based modalities, that allow a selective genetic manipulation in vivo, are powerful tools for personalized medicine, enabling downregulation or expression of relevant proteins. Yet, RNA-based therapeutics requires a delivery modality to facilitate the stability, uptake and intracellular release of the RNA molecules. The use of lipid nanoparticles as a drug delivery approach improves the payloads' stability, pharmacokinetics, bio-distribution and therapeutic benefit while reducing side effects. Moreover, a wide variety of targeting moieties allow a precise and modular manipulation of gene expression, together with the ability to identify and selectively affect disease-relevant leukocytes-subsets. Altogether, RNA-based therapeutics, targeting leukocytes subsets, is believed to be one of the most promising therapeutic concepts of the near future, addressing pressing issues in cancer and inflammation heterogeneity.