Genetically modified (GM) vaccines and vectors that are derived from orthopoxviruses (OPXV) have been successful in managing many veterinary diseases but have not progressed beyond clinical trials in protecting against human diseases. The new CRISPR/Cas9 genome editing tool -derived from bacteria adaptive immune system, if applied in a responsible and safe manner, can advance OPXV-derived GM vaccines beyond clinical trials. CRISPR/Cas9´s efficiency, versatility, precision and low-cost endows it with numerous advantages over the classical methods of genetic modification. The recent adaptation of CRISPR/Cas9 to edit the Vaccinia virus -OPXV prototype strain, provides the opportunity to apply the technology to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors. These hindrances include genome and transgene stability; predictability of attenuation; elucidation of factors that influence recombinant MVA vaccines and vectors; as well as host range restriction, which are important biosafety and risk assessment considerations of virus-based GM vaccines and vectors. Research is underway in various fronts to improve and maximize the potential of CRISPR/Cas9, however, this endeavor will be further enhanced by also incorporating important biosafety research components, such as off- and on-target effects, to ensure responsible development of the technology at this early stage.

Okoli, A.; Okeke, M.I.; Tryland, M.; Moens, U. (2018) CRISPR/Cas9—Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development. Viruses, 10, 50. Open access.

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