Viral Replicon Systems and Their Biosafety Aspects.

Introduction: Viral RNA replicons are self-amplifying RNA molecules generated by deleting genetic information of one or multiple structural proteins of wild-type viruses. Remaining viral RNA is used as such (naked replicon) or packaged into a viral replicon particle (VRP), whereby missing genes or proteins are supplied via production cells. Since replicons mostly originate from pathogenic wild-type viruses, careful risk consideration is crucial. Methods: A literature review was performed compiling information on potential biosafety risks of replicons originating from positive- and negative-sense single-stranded RNA viruses (except retroviruses). Results: For naked replicons, risk considerations included genome integration, persistence in host cells, generation of virus-like vesicles, and off-target effects. For VRP, the main risk consideration was formation of primary replication competent virus (RCV) as a result of recombination or complementation. To limit the risks, mostly measures aiming at reducing the likelihood of RCV formation have been described. Also, modifying viral proteins in such a way that they do not exhibit hazardous characteristics in the unlikely event of RCV formation has been reported. Discussion and Conclusion: Despite multiple approaches developed to reduce the likelihood of RCV formation, scientific uncertainty remains on the actual contribution of the measures and on limitations to test their effectiveness. In contrast, even though effectiveness of each individual measure is unclear, using multiple measures on different aspects of the system may create a solid barrier. Risk considerations identified in the current study can also be used to support risk group assignment of replicon constructs based on a purely synthetic design.

RNA interference to combat the Asian tiger mosquito in Europe: A pathway from design of an innovative vector control tool to its application.

The Asian tiger mosquito Aedes albopictus is currently spreading across Europe, facilitated by climate change and global transportation. It is a vector of arboviruses causing human diseases such as chikungunya, dengue hemorrhagic fever and Zika fever. For the majority of these diseases, no vaccines or therapeutics are available. Options for the control of Ae. albopictus are limited by European regulations introduced to protect biodiversity by restricting or phasing out the use of pesticides, genetically modified organisms (GMOs) or products of genome editing. Alternative solutions are thus urgently needed to avoid a future scenario in which Europe faces a choice between prioritizing human health or biodiversity when it comes to Aedes-vectored pathogens. To ensure regulatory compliance and public acceptance, these solutions should preferably not be based on chemicals or GMOs and must be cost-efficient and specific. The present review aims to synthesize available evidence on RNAi-based mosquito vector control and its potential for application in the European Union. The recent literature has identified some potential target sites in Ae. albopictus and formulations for delivery. However, we found little information concerning non-target effects on the environment or human health, on social aspects, regulatory frameworks, or on management perspectives. We propose optimal designs for RNAi-based vector control tools against Ae. albopictus (target product profiles), discuss their efficacy and reflect on potential risks to environmental health and the importance of societal aspects. The roadmap from design to application will provide readers with a comprehensive perspective on the application of emerging RNAi-based vector control tools for the suppression of Ae. albopictus populations with special focus on Europe.

Biotechnologically produced chitosan for nanoscale products. A legal analysis.

Conventionally, chitosans are derived from shrimp and other crustacean shells. Biotechnology offers an alternative route to produce chitosans and more importantly, specific chitosan structures tailored to the needs of a diversity of industries. However, for biotech chitosans and products thereof to be commercialised, legislation should not create a burden. Here, the requirements of the EU regulatory framework have been analysed for the entire chain from research to development and production of several potential applications including nanomaterials. The animal or biotechnological origin leads to specific requirements in production of the raw material. No EU legislation dedicated to nanomaterials has been adopted. Instead, products are governed under the respective existing product legislation subject to extra requirements for safety assessment. While a knowledge gap exists on hazards related to nanomaterials in general, there is a need to establish realistic regulatory study designs to assess the safety of specific products. Furthermore, as many of the existing chitosan applications are not considered nanomaterials, it would be discriminatory to treat biotechnology derived products differently.

The current state of GMO governance: are we ready for GM animals?

Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology.