A genetically synthetic protein-based cationic polymer for siRNA delivery

Abstract

In recent years, a large number of researchers have paid much attention on small interfering RNA (siRNA) after the advent of RNA interference technology, which has been harnessed as an efficient way of sequence-specific gene silencing in gene therapy, enables elucidation of gene functions, and the identification of new drug targets. Despite tremendous progress has been made in novel delivery systems and vectors via formulation of polyplexes and conjugations, such as cationic polymers (LPEI, BPEI), cationic liposome (DOTAP), peptides (CPP), unmet needs still exist. Many cationic agents used for condensing siRNA often exhibits severe cytotoxicity, which limits clinical applications, and is obliged to be handled. Thus great interest in searching for novel and sophisticated polymeric vectors has been spurred. Herein we proposed a genetically synthetic protein-based polymer, which is also referred to as elastin-like polypeptides (ELPs) excerpted from human tropoelastin highly repetitive sequence, Val-Pro-Gly-Xaa-Gly, where the "guest residue" Xaa is any amino acid except Pro. Thus, if we alternate the "guest residue" Xaa to Lys or Arg, to a significant extent, it can emerge as a powerful cationic polymer for siRNA delivery carrier, and hopefully it will be put into practice in the near future.