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Are we ready for genome editing in human embryos for clinical purposes

Published on May 1, 2019in European Journal of Medical Genetics2.02
· DOI :10.1016/j.ejmg.2019.103682
Joyce C. Harper46
Estimated H-index: 46
(UCL: University College London),
Gerald Schatten71
Estimated H-index: 71
(University of Pittsburgh)
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Abstract
Abstract Perhaps the two most significant pioneering biomedical discoveries with immediate clinical implications during the past forty years have been the advent of assisted reproductive technologies (ART) and the genetics revolution. ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection and preimplantation genetic testing, has resulted in the birth of more than 8 million children, and the pioneer of IVF, Professor Bob Edwards, was awarded the 2010 Nobel Prize. The genetics revolution has resulted in our genomes being sequenced and many of the molecular mechanisms understood, and technologies for genomic editing have been developed. With the combination of nearly routine ART protocols for healthy conceptions together with almost error-free, inexpensive and simple methods for genetic modification, the question “ Are we ready for genome editing in human embryos for clinical purposes? ” was debated at the 5th congress on controversies in preconception, preimplantation and Prenatal Genetic Diagnosis, in collaboration with the Ovarian Club Meeting, in November 2018 in Paris. The co-authors each presented scientific, medical and bioethical backgrounds, and the debate was chaired by Professor Alan Handyside. In this paper, we consider whether genome editing is safe and ethical. We conclude that we are currently not ready for genome editing to be used in human embryos for clinical purposes, and we call for a global debate to determine if and when this technology could be used in ART. ‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬
  • References (29)
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References29
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Published on Jan 22, 2019in Nature Communications11.88
Jonathan Strecker6
Estimated H-index: 6
,
Sara R. Jones39
Estimated H-index: 39
+ 6 AuthorsFeng Zhang104
Estimated H-index: 104
The type-V CRISPR effector Cas12b (formerly known as C2c1) has been challenging to develop for genome editing in human cells, at least in part due to the high temperature requirement of the characterized family members. Here we explore the diversity of the Cas12b family and identify a promising candidate for human gene editing from Bacillus hisashii, BhCas12b. However, at 37 °C, wild-type BhCas12b preferentially nicks the non-target DNA strand instead of forming a double strand break, leading to...
Published on Jan 1, 2019in Developmental Biology2.94
Maryam Mehravar1
Estimated H-index: 1
(Avicenna Research Institute),
Abolfazl Shirazi13
Estimated H-index: 13
(Shahrekord University)
+ 1 AuthorsMehdi Banan9
Estimated H-index: 9
Abstract The CRISPR/Cas9 system is a rapid, simple, and often extremely efficient gene editing method. This method has been used in a variety of organisms and cell types over the past several years. However, using this technology for generating gene-edited animals involves a number of obstacles. One such obstacle is mosaicism, which is common in founder animals. This is especially the case when the CRISPR/Cas9 system is used in embryos. Here we review the pros and cons of mosaic mutations of gen...
Published on Dec 1, 2018in Nature Communications11.88
Zhen Liu11
Estimated H-index: 11
(CAS: Chinese Academy of Sciences),
Zongyang Lu3
Estimated H-index: 3
(ShanghaiTech University)
+ 10 AuthorsYu Zhang4
Estimated H-index: 4
(ShanghaiTech University)
A recently developed adenine base editor (ABE) efficiently converts A to G and is potentially useful for clinical applications. However, its precision and efficiency in vivo remains to be addressed. Here we achieve A-to-G conversion in vivo at frequencies up to 100% by microinjection of ABE mRNA together with sgRNAs. We then generate mouse models harboring clinically relevant mutations at Ar and Hoxd13, which recapitulates respective clinical defects. Furthermore, we achieve both C-to-T and A-to...
Published on Sep 2, 2018in Anthropology & Medicine1.09
Susanna Graham (University of Cambridge)
ABSTRACTDrawing upon the narratives of 23 single heterosexual women in the UK thinking about and pursuing motherhood through sperm donation, this paper explores how solo motherhood can be construed as a ‘risk’ to the identity of a ‘good’ mother. It shows how, for these women, solo motherhood was a departure from an imagined life of having a child within the context of a stable relationship and was a prospect viewed with much ambivalence and uncertainty. Choosing to become a single mother challen...
Published on Jul 12, 2018in Frontiers in Pharmacology3.85
Laurence O. W. Wilson2
Estimated H-index: 2
(CSIRO: Commonwealth Scientific and Industrial Research Organisation),
Aidan R. O’Brien1
Estimated H-index: 1
(ANU: Australian National University),
Denis C. Bauer13
Estimated H-index: 13
(CSIRO: Commonwealth Scientific and Industrial Research Organisation)
Recent years have seen the development of computational tools to assist researchers in performing CRISPR-Cas9 experiment optimally. More specifically, these tools aim to maximize on-target activity (guide efficiency) while also minimizing potential off-target effects (guide specificity) by analyzing the features of the target site. Nonetheless, currently available tools cannot robustly predict experimental success as prediction accuracy depends on the approximations of the underlying model and h...
Published on Jul 1, 2018in Reproduction3.13
Alan H. Handyside50
Estimated H-index: 50
(UKC: University of Kent)
The first pregnancies and live births following IVF and preimplantation genetic testing (PGT), formerly known as preimplantation genetic diagnosis (PGD), were reported in 1990, almost 30 years ago, in several couples at risk of X-linked inherited conditions, which typically only affect boys inheriting the X chromosome with the affected gene from their carrier mothers. At that time, it was only possible to identify the sex of the embryo by amplifying a Y-linked repeat sequence in single cells bio...
Published on Mar 1, 2018in Journal of Medical Screening2.13
Joyce C. Harper46
Estimated H-index: 46
(UCL: University College London)
Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selectin...
Published on Sep 1, 2017in Cell Stem Cell21.46
Xiao-Jiang Li61
Estimated H-index: 61
(Emory University),
Zhuchi Tu7
Estimated H-index: 7
(JNU: Jinan University)
+ 1 AuthorsLi Shihua76
Estimated H-index: 76
(Emory University)
Off-target effects and mosaicism are major concerns for applying CRISPR-Cas9 to correct genetic mutations. A recent article in Nature by Ma et al. (2017) uses an elegant CRISPR-Cas9 approach that repairs a genetic mutation in human embryos with negligible mosaicism and no off-target effects, bringing this editing tool closer to clinical application.
Published on Aug 1, 2017in Translational Andrology and Urology
Ryan Flannigan3
Estimated H-index: 3
,
Phil Bach6
Estimated H-index: 6
,
Peter N. Schlegel57
Estimated H-index: 57
Microdissection testicular sperm extraction (microTESE) is considered the gold standard method for surgical sperm retrieval among patients with non-obstructive azoospermia (NOA). In this review, we will discuss the optimal evaluation of NOA patients and strategies to medically optimize NOA patients prior to microTESE. In addition, we will also discuss technical principles and pearls to maximize the chances of successful sperm retrieval, sperm retrieval rates (SRR) based upon testicular histology...
Published on Aug 1, 2017in Nature43.07
Hong Ma27
Estimated H-index: 27
(Oregon National Primate Research Center),
Nuria Marti-Gutierrez1
Estimated H-index: 1
(OHSU: Oregon Health & Science University)
+ 28 AuthorsRiffat Ahmed10
Estimated H-index: 10
(OHSU: Oregon Health & Science University)
CRISPR–Cas9 genome editing is used to induce a DNA repair response and correct a disease-causing heterozygous mutation in human embryos with reduced mosaicism and preferential repair using the wild-type copy of the gene.
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