Presentation by Filipa Ferraz de Oliveira (European Research Council, Ethics sector, Brussels, Belgium) on the Animal issues raised by genome editing technology at the ARRIGE Kick-Off meeting. ARRIGE Kick-Off meeting was held on 23 March 2018 at the Région Île-de-France Parliament, in Paris, France.
Today, the scientific journal Nature Methods, retracted a publication by Schaefer et al. that appeared on 30 May 2017 claiming to have found numerous unexpected mutations after a CRISPR-Cas9 experiment in vivo, in mice. The unexpectedly high number of off-target mutations reported in the study caught the field by surprise, where noone else appeared to have found similar data. However, this was a most relevant issue, should have been true, directly affecting the expectatives of the CRISPR-derived uses and applications. That publication negatively impacted in the nascent field of genome editing applications, particularly those related to biomedicine, to develop innovative gene therapy approaches. However, almost immediately, many groups around the world expressed doubts and critized the experimental design of the study and the interpretation of the observed results. Soon thereafter, several manuscripts and publications were released with more plausible alternative explanations (low number of cases analyzed, mice genetically unrelated, persisting Cas9 expression…). Anyone interested to review a timeline of events associated with this publication can visit the corresponding section of the CRISPR web at the CNB-CSIC, maintained by Lluis Montoliu.
The first phrase of the Editorial Retraction note explains this decision: “This paper is being retracted because the genomic variants observed by the authors in two CRISPR-treated mice cannot be conclusively attributed to CRISPR–Cas9.“. In other words, the most plausible explanation for the original findings were the underlying genetic differences between control and experimental mice, in principle derived from the same genetic background, but in reality selected from unrelated, and hence, genetically different, mouse colonies.