Viral replicon systems and their biosafety aspects –Inventory and description of viral replicon systems and characteristics relevant for risk assessment

Much attention is being paid to the development and application of viral replicons, both as an aid in (fundamental) laboratory research and in medical applications in vaccine and cancer research. Replicons can still replicate their (viral) genome after an infection of a cell, but they are unable to form new virus particles and spread further. For this purpose, one or more genes encoding the structural proteins have been deleted or replaced by a transgene (‘gene-of-interest’). By providing the structural destruction separately (in trans), viral replicon particles can be generated that can infect cells once. Examples of replicons are the self-amplifying mRNA vaccines against COVID-19 and influenza, which are currently under development.

In view of the increase in the number of requests for advice on assigning containment levels for work with replicons, COGEM commissioned a research project on various aspects of replicon systems. This research was carried out by Perseus B.V. and focused on the question of which replicon systems are under development and which strategies have been developed to improve the biosafety of replicons.

Based on literature research, the great diversity of viral replicon systems, derived from positive- or negative-sense single stranded RNA viruses, is described. Despite the great diversity, a number of common aspects with regard to possible environmental risks could be identified. The report describes various strategies to mitigate these risks and includes a schedule that can be used as a guideline for possible downscaling of viral replicon systems.

The COGEM research report can be found under the button ‘download publication’. The generic COGEM advice that has been drawn up on basis of these results can be found here.