Polyester-based nanoparticles for nucleic acid delivery

Abstract

Gene therapy is promising for the treatment of inherited diseases and complex diseases such as chronic infections and cancer. The advancement in science and technology has extended the scope of gene therapy from gene transfer to the delivery of a variety of nucleic acids such as mRNA, antisense oligonucleotides (ASOs), siRNA and miRNA. Nanoparticle delivery systems can efficiently protect the nucleic acids from enzymatic degradation and immune recognition, facilitate intracellular transportation and assist the nucleic acid in escaping from renal and hepatic clearance, thus achieve sustained delivery to the target tissue. Aliphatic polyesters such as PLA, PLGA, PCL and PHB have entered clinic for decades for making implantable medical devices such as surgical meshes, sutures, screws, tissue repair patches and filling agents; and have been actively investigated for drug and gene delivery due to the excellent degradability and biocompatibility. Cationic polyester nanospheres, micelles and dendrimers which can efficiently condense and deliver nucleic acids have been synthesized via methods such as physical mixing, chemical conjugation and copolymerization of polyesters and cationic molecules.