Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy
Authors: Matthew L Oliver
Charles A Gersbach
Christopher E Nelson
Joel D Bohning
Jacqueline N Robinson-Hamm
Karen Bulaklak
Yaoying Wu
Ruth M Castellanos Rivera
Matthew P Gemberling
Joel H Collier
Matthew A Waller
Aravind Asokan
Journal: Nature medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Duchenne muscular dystrophy; genome editing; CRISPR; mdx mouse model; adeno-associated virus
Affiliations: Department of Biomedical Engineering, Duke University, Durham, NC, USA., Center for Genomic and Computational Biology, Duke University, Durham, NC, USA., Gene Therapy Center, University of North Carolina Chapel Hill, Chapel Hill, NC, USA., Department of Surgery, Duke University Medical Center, Durham, NC, USA., Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA., Department of Biomedical Engineering, Duke University, Durham, NC, USA. ., Center for Genomic and Computational Biology, Duke University, Durham, NC, USA. ., Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA. .

Abstract:  Duchenne muscular dystrophy (DMD) is a monogenic disorder and a candidate for therapeutic genome editing. There have been several recent reports of genome editing in preclinical models of Duchenne muscular dystrophy1-6, however, the long-term persistence and safety of these genome editing approaches have not been addressed. Here we show that genome editing and dystrophin protein restoration is sustained in the mdx mouse model of Duchenne muscular dystrophy for 1 year after a single intravenous administration of an adeno-associated virus that encodes CRISPR (AAV-CRISPR). We also show that AAV-CRISPR is immunogenic when administered to adult mice7; however, humoral and cellular immune responses can be avoided by treating neonatal mice. Additionally, we describe unintended genome and transcript alterations induced by AAV-CRISPR that should be considered for the development of AAV-CRISPR as a therapeutic approach. This study shows the potential of AAV-CRISPR for permanent genome corrections and highlights aspects of host response and alternative genome editing outcomes that require further study. 

Retracted: No

PubPeer comments:
 https: doi.org 10.5013 IJSSST.a.19.06.46 **1 Forged authorship, _i.e._ usurped or theft of authorsu2019 names and affiliations**: The names of Bertrand Chapron and Alexander Babanin, which were on the [original list of the authors] of this manuscript, were unduly used by the 2 main authors Tim Chen and C.Y.J. Chen; so were their respective affiliations to the _Laboratoire d Ocu00e9anographie Physique et Spatiale, IFREMER (Plouzanu00e9, France)_ and to the _Department of Infrastructure Engineering, University of Melbourne_ -Australia. Neither Bertrand Chapron nor Alexander Babanin took part in this publication, which is totally outside their scientific fields of expertise; neither did they give their consent to be the co-authors. They had no prior contact with Tim Chen and CYJ Chen in any shape or form, until they became aware that their names were being unduly cited by the two above-cited authors. **2 Misleading practice of the journal**: The names of Bertrand Chapron and Alexander Babanin were taciturnly removed from this paper by the journal after the 2 authors contacted the editor of _International Journal of Simulation: Systems, Science and Technology_ in late January 2021 to report the usurpation of their identities. No corrigendum was published by the journal even though the 2 authors B. Chapron and A. Babanin requested it. **3 Affiliations and email address(es) of the corresponding author(s)**: **3.1.** The academic affiliation of the corresponding author Tim Chen (timchen@tdtu.edu.vn) is: _Faculty of Information Technology, Ton Duc Thang University (TDTU), Ho Chi Minh City, Vietnam_. Ifremer contacted TDTU in January 2021 to report the usurpation of Bertrand Chapronu2019s and Alexander Babaninu2019s identities. TDTU led its own investigation into Tim Chenu2019s activities. However, Ifremer is not in a legal position to disclose the outcome of TDTUu2019s investigation. **3.2.** The affiliations of the corresponding author C.Y.J. Chen (jc343965@gmail.com) are: _Industrial Technology Research Institute, Hsinchu, Taiwan_ and _The Department of Artificial Intelligence, University of Maryland, Maryland_-USA. C.Y.J. Chen s affiliation to the University of Maryland-USA is erroneous. According to the information available on internet, there is no _Department of Artificial Intelligence_ at the University of Maryland-USA. The author C.Y.J. Chen exhibited 29 different academic affiliations in different institutes and or universities in 15 different countries (_i.e._ Bangladesh, Nigeria, Saudi Arabia, United States, Papua New Guinea, Taiwan, United Kingdom, Brasilia, Australia, China, Russia, Kazakhstan, Vietnam, Spain, Egypt) for the 66 papers (at least) published between 2018 and 2021 in which he is a co-author with Tim Chen (timchen@tdtu.edu.vn). **4 Similarities with any other studies**: Compilatio software allowed to detect a rather high overall similarity of 45% (SI) matching with 3 other related articles by the same 2 main authors T. Chen and C.Y.J. Chen: u00b0 https: doi.org 10.32604 sv.2019.04233 with a matching similarity of 35%; u00b0 https: doi.org 10.22158 ees.v1n1p33 with a matching similarity of 31%; u00b0 https: doi.org 10.1007 s10846-020-01149-5 with a matching similarity 17%. **5 Related papers by the same two authors Tim Chen and CYJ alias John Chen**: Questionable practices in some other papers written by Tim Chen and C.Y.J. alias John Chen, including a withdrawn paper, are addressed in several posts that are part of the [IFREMER_2021_CC] scientific integrity case handled by [Ifremer] ; contact email address: [ddis@ifremer.fr](mailto:ddis@ifremer.fr). , 
 _Retraction Watch_ has reported on February 3rd, 2022: u201c[French ocean institute goes public about authors who forged their researchersu2019 names] .u201d , 
 #1  https: doi.org 10.32604 sv.2019.04233 with a matching similarity of 35%; Does Compilatio software assess the similarity of mathematical or pseudo-mathematical derivations? ![file] ---------------------------- From  Synthesized AI LMI-based Criterion for Mechanical Systems ([Chen et al 2019] ): ![file] The other paper contains an additional section 3, purporting to apply the Evolved Bat Algorithm to a mechanical problem (without doing so) and consisting of gibberish; that is the main difference. Both papers introduce and claim credit for [Tsai s EBA] . ,