Two new peer-reviewed papers added on unexpected outcomes from gene editing

We've added two papers to our list of scientific research articles with findings that support the need for stringent regulation of gene-edited plants, animals, and foods. Our summaries and analyses are below.

We know that some readers have been using this list as a reference document, so we've marked the new additions with "[UPDATE 4 Feb 2020]" so you can clearly see what's new.

We will continue to update this document as new research comes out.
7) [UPDATE 4 Feb 2020] Smits AH et al (2019). Biological plasticity rescues target activity in CRISPR knock outs. Nat Methods 16, 1087–1093.

This study in human cells revealed a major unintended effect from the CRISPR-Cas9 gene-editing tool. CRISPR edits intended to knock out the function of a gene failed to do so. Instead, proteins were still produced from the damaged genes. Many of those proteins were still functional, but they were also mutant,[28] which means they could gain a novel function, with unknown consequences.

GMWatch comment: The study has major implications for the food safety of gene-edited plants, as they could turn out to be unexpectedly toxic or allergenic. CRISPR-edited plants with gene knockouts should be subjected to stringent safety checks, as they could contain new proteins or compounds that pose a food safety risk. These include the non-browning mushroom that has been de-regulated in the US.

The developer of the mushroom stated that it did not need to be regulated since it was free from transgenes (genes inserted from another organism) and only contained “small deletions in a specific gene”.

However, these findings, as well as those of Tuladhar and colleagues (above) suggest that the developer and the US regulators should revisit their assessment. The “small deletion” in a single gene in the CRISPR-edited mushroom may have led to the production of new proteins and altered biochemistry that put consumer health at risk.

Further reading: GMWatch, Researchers assumed CRISPR-mediated disruption of genes was turning them off – but they were wrong. 11 Jan 2020.

8) [UPDATE 4 Feb 2020] Sansbury BM et al (2019). Understanding the diversity of genetic outcomes from CRISPR-Cas generated homology-directed repair. Commun Biol 2, 1–10.

This study reported that a new tool for rapidly analyzing CRISPR edits has revealed the frequent production of unintended edits around the site of the intended cut in the DNA. Eric Kmiec, the lead author, commented that this is different from the risk of CRISPR causing "off-target" mutations by drifting from the intended site and making random cuts across the genome.

GMWatch comment: The conclusion that must be drawn is that improving the precision of the initial CRISPR edit cannot solve this problem.

Further reading: GMWatch, New tool for rapidly analyzing CRISPR edits reveals frequent unintended edits. 6 Jan 2020.