Nature Methods retracts publication that claimed to have found numerous unexpected mutations after CRISPR-Cas9 experiment in vivo

Nature Methods Editorial retraction of the publication: Unexpected mutations after CRISPR-Cas9 editing in vivo. Schaefer KA, Wu WH, Colgan DF, Tsang SH, Bassuk AG, Mahajan VB. Nat Methods. 2017 May 30;14(6):547-548.

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.

Eventually, today, Nature Methods adopted an Editorial decision and retracted this publication, with the agreement of two of its authors and the disagreement of the rest, including the first and last author of the study. This was the most logical and expected decision. Simultaneously, Nature Methods has released five different responses from five independent laboratories, experts in the field of genome editing, with alternative explanations for the original study, now retracted.

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.

Basic information about ARRIGE and how to join

ARRIGE Presentation document (March 2018) – Working document

Basic information about the ARRIGE initiative can be obtained from this Presentation document (March 2014), prepared by the ARRIGE Steering Committee. This is a working document.

How to join ARRIGE?
The ARRIGE initiative was launched in Paris on 23 March 2018. However, the association does not exist yet, formally speaking. Currently, we are working hard preparing all the administrative and legal paperwork required to officially register ARRIGE as an international non-for-profit organization in France, with the great help and commitment from members of the INSERM Ethics Committee. In the meantime we have activated a communication channel, a discussion email list, where all interested individuals and organizations that would like to help and contribute to the foundation of ARRIGE, and/or to eventually become members of the association, are kindly invited to join. If you would like to join ARRIGE please send us a message to join@arrige.org and we will register your email address in the ARRIGE discussion email list.

The CRISPR web at CNB: a web repository of CRISPR information and publications

The CRISPR-Cas system from bacteria transformed into a most efficient genome editing tool.

Anyone interested in the prokaryotic origins of the CRISPR systems and their transformation into the most efficient ever known genome editing tools should consider visiting this CRISPR web page at CNB-CSIC, maintained by Lluis Montoliu. This is a most useful and regularly updated web repository of publications, information, history, protocols, procedures, talks, videos, etc… all about CRISPR and their use as genome editing tool in a variety of applications.

ARRIGE in Spanish: interview to Francisco J. M. Mojica on the origins of CRISPR


In this short video interview (in Spanish), as a brief summary of a much longer text in El País newspaper, the journalist visits Francisco J. M. Mojica (University of Alicante, Spain) who shows the saltworks of Santa Pola, near Alicante, where he first described the CRISPR arrays from an archaea, 25 years ago. Francis Mojica coined the name of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) at the end of 2001 and, two years later discovered that CRISPR were part of an adaptive immune system developed by prokaryotes (bacteria and archaea) as a defense mechanism against the virus (bacteriophages) and other molecules of genetic material that infected  or visited them. Ten years later, the CRISPR bacterial immune system was transformed into an efficient genome editing tool.

ARRIGE in French: interview to Sylvain Moineau and Christian Siatka on CRISPR basics


The last (November 2017) annual meeting of the SFG (Société Française de Génétique / French Genetics Society) in Montpellier (France)  was devoted to CRISPR : The CRISPR revolution: from bacterial immunity to functional genomics. The meeting organizers (among which one of the members of the ARRIGE Steering Committee, Cyril Sarrauste de Menthière) made an interview (in French) to Sylvain Moineau (Université Laval, Québec, Canada; one of the pioneers of the CRISPR systems in bacteria) and Christian Siatka (Director of the “Ecole de l’ADN”). This video, now available from the YouTube platform is here enclosed, within the ARRIGE blog, for educational purposes