There are several barriers to gene delivery. One of the biggest challenges is the design of appropriate vectors. Currently, nonviral vectors have received significant attention because of low toxicity, potential for tissue specificity, stability during storage, lack of immunogenicity, and relatively low production cost. Despite the high efficiency of viral vectors, they show limited clinical applications because of potentially fatal adverse effects and because of the likelihood of the immune response shutting down the transgene expression system. Nonviral technologies comprise plasmid-based expression systems harboring a gene that encodes a therapeutic protein along with a synthetic gene delivery system. This review provides a broad perspective on recent improvements in the development of four kinds of nonviral vectors that are based on polymers, peptides, lipids, and DNA and discusses the cytotoxicity associated with gene therapy.
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