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Welcome to the HSEBiological AgentseBulletin

Welcome to this special edition of the Biological Agents eBulletin. This information is aimed at researchers and genetic modification safety committee members involved in contained use of genetically modified organisms (GMOs), using gene editing. /

‘Gene editing’ and ‘gene drive’

Recent developments have shown that nuclease-based systems designed for gene editing can, in some configurations, comprise synthetic selfish DNA elements or “gene drive” systems. This possibility should be considered during the planning and risk assessment process for such experiments.
Selfish DNA systems can spread through a population without having to confer a fitness benefit to individual carriers. Recent advances in molecular biology provide an array of techniques for editing genes and engineering gene drive mechanisms (eg TALENS and CRISPR based techniques). The CRISPR-Cas9 gene-editing method has recently been used to create endonuclease-based gene drive systems that were able to spread rapidly in insect populations. Such systems have important applications for addressing global problems in public health, sustainable agriculture and environmental management.
Most applications of gene editing techniques are undertaken in cell culture and the resulting engineered cells present negligible risks to human health or the environment. Where the intention is to use gene editing techniques to modify whole organisms (eg animals, including nematodes and insects, or plants), and eukaryotic microorganisms (eg yeast), the potency of this new technology means that users should make additional consideration of the potential environmental risks associated with synthesis and accidental release or escape of a genetic element that may rapidly spread in wild type populations. In such cases, there is a need for the safety aspects of each application to be considered on a case by case basis.

Strategic and tiered approach to assessment of gene editing research

This case by case assessment should involve a tiered strategic approach. In the first instance, the use of CRISPR-Cas9 for genome editing in the vast majority of situations, will not require system configurations that could lead to gene drive. Configurations that would raise concerns in this regard include:

Co-location of the gene encoding CRISPR-Cas9 with the targeting sequence (guide RNA) in a single heritable unit
Designs in which the Cas9 gene and/or guide RNA are expected to insert into the target sequence (“homing” behaviour)

Secondly, where one of the factors above is required, “non-autonomous” configurations should be considered where the potential for super-Mendelian inheritance is lost in subsequent generations (eg due to segregation of system components). Finally, if alternatives cannot be used, and autonomous systems are planned, additional containment and control measures may be required. These will vary depending on the specific species, applications and circumstances, but are likely to be enhanced compared to otherwise-similar GMOs of the same species that lack potential synthetic selfish DNA elements.
Information generated from development of gene-drives in contained use can then be used to inform applications for experimental releases. This step wise and case by case approach is advocated in recent publications in Science.

Forthcoming events

Further analysis by the USA’s National Academy is underway ‘Gene Drive Research in Non-Human Organisms: Recommendations for Responsible Conduct’, the outcome of which may inform the approach to containment in the UK.
Given the importance and potential of this new approach, the Scientific Advisory Committee for Genetic Modification, which has contributed to drafting of the eBulletin, is considering this topic as an agenda item for a joint meeting with the Advisory Committee for Releases into the Environment towards the end of 2016. This will be used to review advances by experts in the field.

Welcome to the Hsebiological Agentsebulletin