It was the night before Christmas … no, it was not. Rather, it was the day before the federal election was called:
“The day before the Federal election was called, the Government quietly announced changes to Australia’s Gene Technology Regulations that will allow a raft of new genetically modified (GM) animals, plants and microbes to enter our environment and food chain with no safety assessment and potentially no labelling. These include super-muscled pigs, non-browning mushrooms, and wheat with powdery mildew-resistance. The deregulation comes as a new study adds to the growing body of evidencethat new GM techniques such as CRISPR are not as safe as claimed. The study found that in 50 per cent of the cells looked at, the use of CRISPR resulted in unexpected effects, including the production of new proteins. There is a risk that these proteins could be novel toxins or allergens. It is vital that GM animals, plants and microbes produced in this way are assessed for safety before being released into our environment and our food chain.”
Here are the articles referred to above:
https://www.nature.com/news/super-muscly-pigs-created-by-small-genetic-tweak-1.17874
https://www.chemistryworld.com/news/crispr-edited-mushroom-dodges-regulation/1010298.article
https://research.csiro.au/gene-editing-workshop/wp-content/uploads/sites/208/2017/12/Felicity-Keiper-Regulatory-Challenges-Presented-by-Genome-Editing.pdf
https://www.biorxiv.org/content/10.1101/583138v1.full
https://institutions.newscientist.com/article/2174149-crispr-gene-editing-is-not-quite-as-precise-and-as-safe-as-thought/
“A study of CRIPSR suggests we shouldn’t rush into trying out CRISPR genome editing inside people’s bodies just yet. The technique can cause big deletions or rearrangements of DNA, says Allan Bradley of the Wellcome Sanger Institute in the UK, meaning some therapies based on CRISPR may not be quite as safe as we thought. The CRISPR genome editing technique is revolutionising biology, enabling us to create new varieties of plants and animals and develop treatments for a wide range of diseases. The CRISPR Cas9 protein works by cutting the DNA of a cell in a specific place. When the cell repairs the damage, a few DNA letters get changed at this spot – an effect that can be exploited to disable genes. At least, that’s how it is supposed to work. But in studies of mice and human cells, Bradley’s team has found that in around a fifth of cells, CRISPR causes deletions or rearrangements more than 100 DNA letters long. These surprising changes are sometimes thousands of letters long.
Cancer risk
This finding is not a problem for the purposes for which CRISPR is currently being used. But some groups are developing treatments that would involve using CRISPR to edit billions of cells inside the human body. If Bradley is right, there’s a chance that a few of these cells might turn cancerous.”
But what is the risk of cancer, between friends? Anyway, the politicians should be able to understand text like this before voting on any aspect of genetically modified organisms:
“The introduction of insertion-deletions (INDELs) by activation of the error-prone non-homologous end-joining (NHEJ) pathway underlies the mechanistic basis of CRISPR/Cas9-directed genome editing. The ability of CRISPR/Cas9 to achieve gene elimination (knockouts) is largely attributed to the emergence of a pre-mature termination codon (PTC) from a frameshift-inducing INDEL that elicits non-sense mediated decay (NMD) of the mutant mRNA. Yet, the impact on gene expression as a consequence of CRISPR/Cas9-introduced INDELs into RNA regulatory sequences has been largely left uninvestigated. By tracking DNA-mRNA-protein relationships in a collection of CRISPR/Cas9-edited cell lines that harbor frameshift-inducing INDELs in various targeted genes, we detected the production of foreign mRNAs or proteins in ~50% of the cell lines. We demonstrate that these aberrant protein products are derived from the introduction of INDELs that promote internal ribosomal entry, convert pseudo-mRNAs into protein encoding molecules, or induce exon skipping by disruption of exon splicing enhancers (ESEs). Our results using CRISPR/Cas9-introduced INDELs reveal facets of an epigenetic genome buffering apparatus that likely evolved to mitigate the impact of such mutations introduced by pathogens and aberrant DNA damage repair, and that more recently pose challenges to manipulating gene expression outcomes using INDEL-based mutagenesis.
https://www.biorxiv.org/content/10.1101/583138v1.full
Authorised by K. W. Grundy
13 Carsten Court, Happy Valley, SA.