Poly(β-amino ester)-based gene delivery systems: From discovery to therapeutic applications

Poly(β-amino ester)s (PβAE) were firstly synthesized in 1983 but only in 2000 these polymers were used for the first time as gene carrier. Thenceforward, due to their excellent gene delivery properties, PβAE were amply explored to afford very effective non-viral vectors. The promising results obtained both in vitro and in vivo studies involving different areas, from cancer therapy to tissue engineering area have aroused a broad interest of the scientific community for this family of biodegradable cationic polymers. This review is the first comprehensive and critical overview of the use of PβAEs as gene carrier. The rational design of PβAEs is a major step aiming to achieve high transfection efficiencies. Moreover, it has been demonstrated that often very small changes in the structure of these polymers have an impressive impact on the transfection efficiency. A critical discussion on the structure performance relationships is presented as well as the outlook for next developments involving these polymers. [Display omitted] •Relationship between physicochemical properties of PβAEs and transfection activity•Types of gene delivery systems based on PβAE•Mechanisms involved in the gene delivery process mediated by PβAE-based systems•Potential therapeutic applications of PβAE-based non-viral vectors