The ARRIGE initiative is featured in this News&Comment article by Eric Smalley in Nature Biotechnology. Indeed a big challenge the one we have ahead of us but an unavoidable one, if we believe in the responsible use of genome editing techniques and in the engagement of all stakeholders that are involved in the process. Hands to work!.
Scheme illustrating the effect of spontaneous mutations and genetic drift responsible for the divergence of animal subcolonies bred independently (Figure from Montoliu and Whitelaw, Transgenic Research, 2018, online May 31).
Bruce Whitelaw (The Roslin Institute, Edinburgh, Scotland, UK) and I, we have just published a commentary in the scientific journal Transgenic Research discussing the case of the Nature Methods paper by Schaefer et al. 2017 who initially reported the identification of numerous off-target sites altered after a genome-editing experiment in vivo, in mice. This paper has recently been retracted by the journal (March 30). As indicated by the authors in this commentary: “The most plausible explanation for the vast majority of the reported unexpected mutations were the expected underlying genetic polymorphisms that normally accumulate in two different colonies of the same mouse strain which occur as a result of spontaneous mutations and genetic drift. Therefore, the reported mutations were most likely not related to CRISPR-Cas9 activity.“
The ARRIGE initiative described in an article published in the second issue of The CRISPR Journal
The ARRIGE initiative is receiving plenty of attention and generating a lot of interest from media and scientific journals. This is the case of The CRISPR Journal, which features a description of the birth of ARRIGE in its second issue. This article is open access. If you want to know more information about the ideas behind the foundation of ARRIGE, how they were shaped, how they developed and crystalized in the recent kick-off meeting in Paris, essentially aiming toward the responsible use of genome editing technologies, you can now simply read this publication.
Final comments, workshop conclusion and next steps by Lluis Montoliu (CNB-CSIC and CIBERER-ISCIII, Madrid, Spain) 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.
Presentation by Lauren Roberts and Louise James (Genetic Alliance UK) on involving patients in the discussion of 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.
Presentation by Béatrice Holtz (LAVOIX, Paris, France) on the Intellectual properties and economic 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.
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.
Presentation by Andreas Kurtz (Charité Hospital, Berlin, Germany and European Group of Ethics, EGE) at the ARRIGE Kick-Off meeting on the Environmental issues raised by genome editing technology. ARRIGE Kick-Off meeting was held on 23 March 2018 at the Région Île-de-France Parliament, in Paris, France.
Presentation by Peter Mills (Nuffield Council on Bioethics, London, UK) on Human 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.
Talk by Hervé Chneiweiss (INSERM Ethics Committee) on the Ethics of the genome editing technologies: presentation of ARRIGE, 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.
Keynote Lecture delivered by Francisco J.M. Mojica (University of Alicante, Spain) on “Setting the stage, where do we stand today with CRISPR technology” and introduced by Lluis Montoliu (CNB-CSIC and CIBERER-ISCIII, Madrid, Spain). ARRIGE Kick-Off meeting was held on 23 March 2018 at the Région Île-de-France Parliament, in Paris, France.
Slides from all presentations delivered by invited guest speakers at the ARRIGE Kick-Off meeting in Paris on 23 March 2018 are ready and available from the corresponding ARRIGE meeting web page.
Slides from all presentations delivered by invited guest speakers at the ARRIGE Kick-Off meeting in Paris on 23 March 2018 are ready and available for consultation from the corresponding ARRIGE meeting web page. These slides have been generously shared by the speakers. Please contact the corresponding speaker if you would like to refer, cite or use any of these materials. Tomorrow we will release the corresponding video files for all sessions and talks at the ARRIGE Kick-Off meeting in Paris.
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.
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.
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.
Yesterday, the US Department of Agriculture (USDA) issued a statement in favour of Plant Breeding Innovation. In the US, the USDA will not regulate genome-edited plants (obtained, for example, through CRISPR tools), as long as they are not pest plants or developed using plant pests, and as long as the resulting genetic alleles could have been also introduced by any traditional breeding technique. In other words, if the CRISPR-derived allele matches an allele previously existing in nature the resulting genome edited plants will not be regulated by USDA. This decision is expected to favour Plant Breeders and researchers in the field of Plant Breeding innovation and is also expected to expedite the development of numerous genome edited plants resistant to drought and diseases or with increased nutritional value.
In Europe some hints towards a similar direction have been seen last January, with the publication of an Opinion by the EU lawyer of the Court of Justice of the European Union on a recent dispute ongoing in France. However, to date, the European Commission, through the European Food and Safety Authority (EFSA) has not yet issued a final decision on the subject.
Francis Mojica, microbiologist from the University of Alicante (Spain) who discovered the CRISPR arrays in archaea, coined the name of CRISPR and first proposed that this was a prokaryote acquired immune defense system.
The recent ARRIGE kick-off meeting in Paris had the pleasure to have Francisco Juan Martínez Mojica (Francis Mojica), microbiologist from the University of Alicante (Spain), delivering the first keynote lecture of the conference. In his very interesting talk, Francis Mojica reviewed the origins of the CRISPR systems in prokaryotes, as part of an ancient acquired immune defense system, and their recent conversion into powerful genome editing tools. He is convinced that we are just beginning to understand the unexpected complexity of bacterial immune systems. CRISPR could be just one of many, yet to be identified and described. There is a great future ahead in the field of Molecular Microbiology for discovering new CRISPR and CRISPR-like systems that could be transformed and adapted for the efficient and safe manipulation of genomes, including the human genome.