Synthetically engineered viruses: Can synthetic chemistry tame the nature?

Gene therapy is a promising tool to tackle challenging diseases at a molecular level. However, delivery of therapeutic nucleic acids to desired tissues and cells with high efficiency, versatility, and safety has been a fundamental technological gap in gene therapy. Viral and nonviral vectors offer advantages and disadvantages that can complement each other. Viral vectors exhibit high transduction efficiency with immunogenicity, mutagenesis, and limited versatility for structural and functional tenability. On the other hand, low transfection efficiency of nonviral vectors undermines their high flexibility for modification, low immunogenicity, and easy preparation. A number of attempts have been made to hybridize viral and nonviral vectors using genetic, physical, and chemical approaches. Synthetic engineering of viral vectors is reviewed here with (1) challenges in viral nucleic acid delivery pathways, in contrast to those of nonviral vectors, (2) design goals of incorporating synthetic molecules of broad types into viral vectors, and (3) methodology to modify and re-formulate viral vectors. Recent advances in synthetically engineered viral vectors for various biomedical applications are also discussed. This review clearly emphasizes the crucial roles of interdisciplinary approaches to developing ideal vectors in order to obtain desired properties for clinical success.