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WIREs Nanomed Nanobiotechnol
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Synthetic virology: engineering viruses for gene delivery

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The success of gene therapy relies heavily on the performance of vectors that can effectively deliver transgenes to desired cell populations. As viruses have evolved to deliver genetic material into cells, a prolific area of research has emerged over the last several decades to leverage the innate properties of viruses as well as to engineer new features into them. Specifically, the field of synthetic virology aims to capitalize on knowledge accrued from fundamental virology research in order to design functionally enhanced gene delivery vectors. The enhanced viral vectors, or ‘bionic’ viruses, feature engineered components, or ‘parts’, that are natural (intrinsic to viruses or from other organisms) and synthetic (such as man‐made polymers or inorganic nanoparticles). Various design strategies—rational, combinatorial, and pseudo‐rational—have been pursued to create the hybrid viruses. The gene delivery vectors of the future will likely criss‐cross the boundaries between natural and synthetic domains to harness the unique strengths afforded by the various functional parts that can be grafted onto virus capsids. Such research endeavors will further expand and enable enhanced control over the functional capacity of these nanoscale devices for biomedicine. WIREs Nanomed Nanobiotechnol 2014, 6:548–558. doi: 10.1002/wnan.1287 This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures
Synthetic virology aims to engineer viruses for gene delivery through the incorporation of natural or synthetic parts. Multiple facets of viruses may need to be enhanced or altered in order to become effective delivery agents for gene therapy applications. Depending on the biomedical application, desired functions of viral vectors may include cell targeting or co‐delivery of small molecule drugs. Synthetic viruses can be created by mixing preexisting viral parts, resulting in formation of chimeric or mosaic capsids. Molecular parts, such as biotin or small molecule drugs, can be attached to virus capsids to act as adaptors or to carry out therapeutic action, respectively. Synthetic parts, such as man‐made polymers and inorganic nanoparticles, can be incorporated into viruses to endow functionalities new to viruses in general. Genetically encoded peptides and proteins can be inserted into viruses, either in rationally chosen sites or randomly throughout the capsid, to impart new functions. Finally, viral properties can be altered through introduction of point mutations scattered throughout the capsid or concentrated in specific capsid domains.
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