ABSTRACT Gene therapy continues to hold promise in treating a variety of inherited and acquired diseases. The great majority of gene therapy trials rely on viral vectors for gene transduction because of their high efficiency. Viruses remain the vector of choice in achieving high efficiency of gene transfer in vivo. Viral vectors, however, depict safety concern unlikely to abate in the near future. Non-viral vectors for gene delivery are receiving increasing attention for application in a broad variety of gene-mediated therapies for humans. In general, non-viral vectors are less toxic and less immunogenic than viral vectors. However, most non-viral methods are less efficient for gene transfer, especially in vivo. Polycationic polymers have been increasingly proposed as potential vectors because of their versatility. Rigidity, hydrophobicity/hydrophilicity, charge density, biodegradability, and molecular weight of the polymer chain are all parameters that in principle can be adjusted to achieve an optimal complexation with DNA. Polymers with repeating polyester bonds in the backbone are structurally versatile, and biodegradable through hydrolysis, and possibly enzymatic digestion at the ester linkages under physiological conditions. These biodegradable polyesters are appealing for biological and pharmaceutical applications because of their potential biocompatibility and similarity to bio-macromolecules such as nucleic acids. In this review, we will focus on characteristics of polyesters as gene delivery carriers, degradation pattern as an essential parameter for reduced toxicity, classification based on its physicochemical properties followed by its success as efficient gene delivery carrier in vitro and in vivo. We will also discuss the conjugation of ligands/charged groups to the side chain of the polyester, constituting target specific moieties such as folate in order to achieve receptor-mediated endocytosis as well as target-specific delivery of DNA. Capable of delivering exogenous genes to a cell nucleus, these cationic polyesters also serve as a valuable model to understand the important characteristics that render a polymer an effective gene carrier
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