Design, Synthesis and Characterization of Novel Polymeric Nanocarriers for Oligonucleotides Delivery

SiRNA and miRNA are short sequences of oligonucleotides that can silence the expression of a targeted gene. This ability places them as highly potent therapeutic approach in cancer targeted therapy. During the past two decades, various attempts were initiated to use siRNAs and miRNAs as therapeutic tools raising many difficulties such as rapid renal clearance, degradation by the body`s RNases, poor cellular penetration, short half-life and aggregation in blood. To overcome these drawbacks, we have designed, synthesized and characterized a library of polyaminated polyglutamic acid (PGAamine) degradable polymers that form a complex with siRNA or miRNA. Our selected PGAamine: siRNA polyplexes exhibited high in vitro and in vivo gene silencing while abrogating toxicity at the concentrations required for the silencing activity.