Synthetic virology

Synthetic Virology is the scientific discipline engaged in the study and engineering of synthetic, man-made Viruses.

It is a multidisciplinary research field, at the crossroad of Virology, Synthetic Biology and Computational Biology, and DNA Nanotechnology from which it borrows and integrates its concepts and methodologies. The two main types of synthetic viruses are 1) live and 2) nanofabricated.

Synthetic viruses can be created from prefabricated inert components which self-assemble upon DNA scaffold patterns. Such synthetic "DNA" viruses mimic the physiology of enveloped viruses, for example by: 1) cell membrane fusion catalysis, 2) cell surface ligand recognition, 3) evasion of cytoplasmic macromolecular crowding, 4) sub-cellular nucleic acid delivery. Nanofabricated synthetic viruses do not contain viral genes and do not have a capacity to replicate.

Live synthetic viruses have their entire genomes constructed from synthetic viral genes, which are then assembled using various methodologies to yield complete viral genomes. The first man-made infectious viruses generated without any natural template were of the Polio virus [1] and the φX174 bacteriophage [2]. With synthetic live viruses, it is not the viruses that are synthesized, but rather their DNA genome at first, both in the case of DNA and RNA viruses, since methodologies for large scale DNA synthesis are much more developed than those for RNA synthesis (for example, there is no RNA-equivalent for PCR). For many virus families the naked genome DNA (or RNA following transcription) is infectious when introduced into a cell. That is, their genome contains all the necessary information to produce new viable viruses. This technology is now being used to investigate novel vaccine strategies[3,4]. The ability to synthesize viruses has far-reaching consequences, since viruses can no longer be regarded as extinct, as long as the information of their genome sequence is known and permissive cells are available. As of March 2014, the full-length genome sequences of 3843 different viruses, including smallpox, are publicly available in an online database maintained by the National Institutes of Health.

Synthetic live virology is in its infancy but already has several applications such as (1) an investigative technology in the study of natural virology and (2) in the engineering of synthetic viruses for biotechnological applications.

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