Non-covalent Encapsulation of siRNA with Cell-Penetrating Peptides

SiRNAs may act as selective and potent therapeutics, but poor deliverability in vivo is a limitation. Among the recently proposed vectors, cell-penetrating peptides (CPPs), also referred as protein transduction domains (PTDs), allow siRNA stabilization and increased cellular uptake. This chapter aims to guide scientists in the preparation and characterization of CPP-siRNA complexes, particularly the evaluation of novel CPPs variants for siRNA encapsulation and delivery. Herein, we present a collection of methods to determine CPP-siRNA interaction, encapsulation, stability, conformation, transfection, and silencing efficiency.