Poly(glycoamidoamine)s: a broad class of carbohydrate-containing polycations for nucleic acid delivery

In the era of nucleic acid therapeutics, there is an urgent need for non-viral delivery vehicles that can cross the extracellular and intracellular barriers and deliver nucleic acids to specific intracellular regions. This paper reviews the development of a subclass of polymer-based delivery vehicles termed poly(glycoamidoamine)s (PGAAs). The general design of this family consists of carbohydrate residues copolymerized with oligoethyleneamine units, which have proven to be an effective motif that promotes polyplex formation, efficient cellular internalization, high gene expression and low cytotoxicity with cultured cell lines and primary cell types. We then discuss the structure–property relationships of the PGAA class of delivery vehicles and studies aimed at understanding the mechanisms involved in cellular internalization and trafficking.