New Fully Biodegradable PEG-Dendrimers: Synthesis and evaluation as siRNA vectors

Gene therapy has been proposed as a powerful approach to treat/prevent several diseases. The original concept consisted in the insertion of exogenous DNA in cells to correct genetic diseases. Currently, the concept has been broadened and other strategies have been reported, such as the promising use of small interfering RNA (siRNA) for the short-term down-regulation of protein expression. However, gene therapy requires the development of clinically suitable, effective, and biocompatible vectors to carry the nucleic acid (NA). Dendrimers are promising NA vectors due to their globular, well-defined, and highly branched, low polydispersity, the presence of terminal groups that can be multifunctionalized with different ligands, and their ability to complex and protect NAs in nanostructures (“dendriplexes”). However, one important drawback of most used dendrimers applied biomedically is their non-degradability under physiological conditions that can result in cytotoxicity induced by non-degradable synthetic materials in the organism. Moreover, biodegradability can be useful since it will favour the siRNA release, leading to higher transfection efficiencies. Here, we report a new family of fully biodegradable, biocompatible, and non-toxic PEG-dendritic block copolymers to act as NA vectors. These novel fully biodegradable PEG-dendrimers allowed the efficient complexation and mediation of siRNA internalization, showing excellent transfection efficiencies