Small interfering RNA (
siRNA) has attracted great attention as a potential new
drug due to its highly sequence-specific gene silencing ability and generality in therapeutic target. However, the medical applications of
siRNA have been severely hindered by the lack of an optimal systemic delivery methodology. This poor delivery performance of
siRNA is mainly caused by its inherent physicochemical properties including short and stiff structure, low charge density and vulnerability to nuclease cleavage. Thus, the successful development of efficient systemic delivery platform for
siRNA is a fundamental requirement necessary to bring
siRNA-based drugs to the market. Herein, we describe some
siRNA delivery methods based on the chemical and structural modifications of delivery materials and
siRNA itself to carry
siRNA therapeutics safely to the targeted place without adverse effects. This review particularly explains the latest progress of chemically and structurally modified
siRNA polymer (poly-
siRNA)-based delivery systems. The stable and compact
siRNA polyplexes, which are formed by poly-
siRNA and different types of
biocompatible materials, can enhance serum stability and target delivery efficiency in vitro and in vivo. In addition, this review provides specific information on poly-
siRNA delivery systems from basics to therapeutic applications in different
animal disease models.