ABSTRACT
The activation of pattern-recognition receptors initiates signalling cascades of immune reactions, and they recognize a series of molecular patterns of the pathogenic ligands. This chapter addresses the use of computational tools to study the immunogenic potential of lipid-based small interfering RNA (siRNA) delivery systems. Utility of siRNA therapeutics is entirely reliant on the ability to deliver siRNA molecules to their site of action, namely the cytosol of the target cells. RNA interference (RNAi) is an evolutionary conserved pathway by which double-stranded RNA (dsRNA) molecules mediate sequence-specific, post-transcriptional gene silencing in cells. A multidisciplinary approach is required to understand the complex mechanisms involved in immunological reactions. However, a collaborative effort should always be sought to provide feedback for improving biocompatibility of components of RNAi therapeutics, robustness of testing methodologies and/or precision of the predictive tools. Conjugation to cholesterol introduces hydrophobicity to the otherwise hydrophilic siRNA, enabling binding to serum albumin and lipoproteins, which improves siRNA pharmacokinetics.
