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Biological agents
eBulletin
Welcome to the HSE Biological Agents eBulletin
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 NonHuman 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.
Further reading

Oye et al (2014), Policy Forum Biotechnology – Regulating Gene Drives, Science, 345,
626-628

Akbari et al (2015), Policy Forum Biotechnology – Safeguarding gene drive
experiments in the laboratory, Science, 349, 927-929

Port et al (2015), Systematic Evaluation of Drosophila CRISPR Tools Reveals Safe and
Robust Alternatives to Autonomous Gene Drives in Basic Research, G3:
Genes|Genomes|Genetics 5(7): 1493-1502

DiCarlo et al. (2015), Safeguarding CRISPR-Cas9 gene drives in yeast, Nature Biotech,
33(12): 1250-1255
Free guidance covering a wide range of biological agents and biosafety
health and safety topics is available on HSE's website.
This bulletin provides a sample of the wide range of information that can be
found under ‘What’s New' on HSE’s website.
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