Gene Editing In Embryos Research Articles

Public Reason, Bioethics, and Public Policy: A Seductive Delusion or Ambitious Aspiration?

Can Rawlsian public reason sufficiently justify public policies that regulate or restrain controversial medical and technological interventions in bioethics (and the broader social world), such as abortion, physician aid-in-dying, CRISPER-cas9 gene editing of embryos, surrogate mothers, pre-implantation genetic diagnosis of eight-cell embryos, and so on? The first part of this essay briefly explicates the central concepts that define Rawlsian political liberalism. The latter half of this essay then demonstrates how a commitment to Rawlsian public reason can ameliorate (not completely resolve) many of the policy disagreements related to bioethically controversial medical interventions today. The goal of public reason is to reduce the size of the disagreement by eliminating features of the disagreement that violate the norms of public reason. The norms of public reason are those norms that are politically necessary to preserve the liberal, pluralistic, democratic character of this society. What remains is reasonable disagreement to be addressed through normal democratic deliberative processes. Specific issues addressed from a public reason perspective include personal responsibility for excessive health costs, the utility of a metaphysical definition of death for organ transplantation, and the moral status of excess embryos generated through IVF and/or their use in medical research.

Data Transmission Security and Legal Regulation in Clinical Application of Human Gene Editing from Perspective of Big Data

Gene editing, as an emerging biotechnology, has enormous potential for application but also brings various risks. Considering the current development status of gene editing technology, the criminal regulation of gene editing is based on the theory of risk criminal law. Ethical safety should be protected as a legal interest, and specific criminalization standards should be used to distinguish gene editing for therapeutic purposes, human embryo gene editing, and other types of gene editing behavior. In view of the many problems currently existing in gene editing legislation, at the legislative level, it is necessary to balance the expansion of legal provisions brought about by risk criminal law theory and the exoneration brought about by allowed risk theory, with administrative legal norms in place, and the criminal law should exercise restraint on emerging technologies; At the judicial level, by referring to the understanding of judicial interpretations of similar crimes, corrections can be made to the elements of criminal composition, serious circumstances, and deficiencies in unit crimes.

Edição genética do embrião humano: tensões e controvérsias de posicionamentos entre cientistas

Abstract Objective: This study analyzed the relation between the position of scientists on embryo editing and the different types of knowledge involved. Methods: A lexical analysis of 151 scientific articles in the PubMed and Web of Science databases was conducted using the IRAMUTEQ software. Results: The results showed that gene editing in embryos is presented in two argumentative branches: the first refers to the editing technique and its possibilities; the second discusses the impacts of these techniques on the public arena. The results demonstrate a consensus regarding the potential of editing; however, dilemmas about its effectiveness were also highlighted. Conclusion: The presence of ethical conflicts with embryo editing among the specialists was evidenced especially regarding the birth of genetically modified babies. Therefore, gene editing is marked by conflicts that are not limited only to biological contexts, but that encompasses different aspects of social life.

A Conformational Restriction Strategy for the Control of CRISPR/Cas Gene Editing with Photoactivatable Guide RNAs.

The CRISPR/Cas system is one of the most powerful tools for gene editing. However, approaches for precise control of genome editing and regulatory events are still desirable. Here, we report the spatiotemporal and efficient control of CRISPR/Cas9- and Cas12a-mediated editing with conformationally restricted guide RNAs (gRNAs). This approach relied on only two or three pre-installed photo-labile substituents followed by an intramolecular cyclization, representing a robust synthetic method in comparison to the heavily modified linear gRNAs that often require extensive screening and time-consuming optimization. This tactic could direct the precise cleavage of the genes encoding green fluorescent protein (GFP) and the vascular endothelial growth factor A (VEGFA) protein within a predefined cutting region without notable editing leakage in live cells. We also achieved light-mediated myostatin (MSTN) gene editing in embryos, wherein a new bow-knot-type gRNA was constructed with excellent OFF/ON switch efficiency. Overall, our work provides a significant new strategy in CRISPR/Cas editing with modified circular gRNAs to precisely manipulate where and when genes are edited.

A Conformational Restriction Strategy for the Control of CRISPR/Cas Gene Editing with Photoactivatable Guide RNAs**

AbstractThe CRISPR/Cas system is one of the most powerful tools for gene editing. However, approaches for precise control of genome editing and regulatory events are still desirable. Here, we report the spatiotemporal and efficient control of CRISPR/Cas9‐ and Cas12a‐mediated editing with conformationally restricted guide RNAs (gRNAs). This approach relied on only two or three pre‐installed photo‐labile substituents followed by an intramolecular cyclization, representing a robust synthetic method in comparison to the heavily modified linear gRNAs that often require extensive screening and time‐consuming optimization. This tactic could direct the precise cleavage of the genes encoding green fluorescent protein (GFP) and the vascular endothelial growth factor A (VEGFA) protein within a predefined cutting region without notable editing leakage in live cells. We also achieved light‐mediated myostatin (MSTN) gene editing in embryos, wherein a new bow‐knot‐type gRNA was constructed with excellent OFF/ON switch efficiency. Overall, our work provides a significant new strategy in CRISPR/Cas editing with modified circular gRNAs to precisely manipulate where and when genes are edited.

After He Jiankui's Case: Chinese Legislative Modifications in Human Embryo Gene Editing.

This article systematically discusses Chinese current legal status and rules for human embryo gene editing in both administrative law and criminal law after several legislative modifications, and further systematically evaluates the values and the defects of these modifications. After He Jiankui's case, Chinese legislators devoted themselves to improve human embryo gene editing legislation. As a result, human embryo gene editing's legal status becomes more determined. Rules for human embryo gene editing in Chinese administrative law have gradually become a complete system centering on "CBL-regulation," and the promulgation of Amendment (XI) to the Criminal Law reconciles the controversy existed in academic circles. Chinese rules for human embryo gene editing are moving from "doubtful development" to "complete legal system."

Effect of Aphidicolin, a Reversible Inhibitor of Eukaryotic Nuclear DNA Replication, on the Production of Genetically Modified Porcine Embryos by CRISPR/Cas9.

Mosaicism is the most important limitation for one-step gene editing in embryos by CRISPR/Cas9 because cuts and repairs sometimes take place after the first DNA replication of the zygote. To try to minimize the risk of mosaicism, in this study a reversible DNA replication inhibitor was used after the release of CRISPR/Cas9 in the cell. There is no previous information on the use of aphidicolin in porcine embryos, so the reversible inhibition of DNA replication and the effect on embryo development of different concentrations of this drug was first evaluated. The effect of incubation with aphidicolin was tested with CRISPR/Cas9 at different concentrations and different delivery methodologies. As a result, the reversible inhibition of DNA replication was observed, and it was concentration dependent. An optimal concentration of 0.5 μM was established and used for subsequent experiments. Following the use of this drug with CRISPR/Cas9, a halving of mosaicism was observed together with a detrimental effect on embryo development. In conclusion, the use of reversible inhibition of DNA replication offers a way to reduce mosaicism. Nevertheless, due to the reduction in embryo development, it would be necessary to reach a balance for its use to be feasible.

Boosting the potential of cattle breeding using molecular biology, genetics, and bioinformatics approaches – a review

Cattle are among the most important farm animals that underwent an intense selection with the aim to increase milk production and to improve growth and meat properties, meanwhile reducing the generation interval allowing for a faster herd turnover. Recently, a shift from traditional breeding methods to breeding based on genetic testing has been observed. In this perspective, we review the techniques of molecular biology, genetics, and bioinformatics that are expected to further boost the agricultural potential of cattle. We discuss embryo selection based on next-generation and Nanopore sequencing and in vitro embryo production, boosting the potential of genetically superior animals. Gene editing of embryos could further speed up the selection process, essentially introducing a change in a single generation. Lastly, we discuss the host-microbiome co-evolution and adaptation. For example, cattle already adapted to low-quality low-cost fodder could be bred to achieve desired properties for the beef and dairy industry. The challenge of breeding and genetic editing is to accompany the selection on desired consumer-oriented traits with the push for sustainability and the adaptation to a changing climate while remaining economically viable. We propose that we are yet to see the limits of what is possible to achieve with modern technology for the cattle of the future; the ultimate goal will be to produce and maintain genetically elite individuals that can sustain the growing demands on the production.

Human embryo gene editing: God's scalpel or Pandora's box?

Gene editing refers to the site-specific modification of the genome, which mainly focuses on basic research, model organism construction and treatment and prevention of disease. Since the first application of CRISPR/Cas9 on the human embryo genome in 2015, the controversy over embryo gene editing (abbreviated as EGE in the following text) has never stopped. At present, the main contradictions focus on (1) ideal application prospects and immature technologies; (2) scientific progress and ethical supervision; and (3) definition of reasonable application scope. In fact, whether the EGE is 'God's scalpel' or 'Pandora's box' depends on the maturity of the technology and ethical supervision. This non-systematic review included English articles in NCBI, technical documents from the Human Fertilization and Embryology Authority as well as reports in the media, which performed from 1980 to 2018 with the following search terms: 'gene editing, human embryo, sequence-specific nuclease (SSN) (CRISPR/Cas, TALENT, ZFN), ethical consideration, gene therapy.' Based on the research status of EGE, this paper summarizes the technical defects and ethical controversies, enumerates the optimization measures and looks forward to the application prospect, aimed at providing some suggestions for the development trend. We should regard the research and development of EGE optimistically, improve and innovate the technology boldly and apply its clinical practice carefully.

Should Parents Design Their Children’s Genome: Some General Arguments and a Confucian Solution

With the emergence of clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) as one of the most promising new gene-editing techniques, scientists are now endeavoring to apply it to various domains. Among all the possible applications, gene editing in human embryos has received the most attention. Against this background, this article carries out a philosophical study on the ethical problems of human embryo gene editing or designing. Arguments against human embryo gene designing include that parents should be prohibited from deciding their children’s future; commodifying children should be prohibited; the natural reproductive process should not be disturbed; and human embryo gene designing might foster discrimination. Arguments for human embryo gene designing include that parents should have the freedom to design their own babies and this freedom should not be limited; designing babies can promote the happy life of the baby; and totally forbidding embryo gene editing would drive the practice underground, where it would be performed illegally. This article analyzes all of these arguments and points out that all of them have some flaws. In order to draw a thoughtful conclusion, we turn to Confucianism and find a new perspective to determine whether designing babies with CRISPR technology is ethically permissible.

Whole Genome Sequencing and Gene Editing of Embryos: Are Infertility Patients Ready? [22S

Whole Genome Sequencing and Gene Editing of Embryos: Are Infertility Patients Ready? [22S

Female subfertility.

Subfertility is common and affects one in six couples, half of whom lack an explanation for their delay in conceiving. Developments in the diagnosis and treatment of subfertility over thepast 50 years have been truly remarkable. Indeed, current generations of couples with subfertility are more fortunate than previous generations, as they have many more opportunities to become parents. The timely access to effective treatment for subfertility is important as many couples have a narrow window of opportunity before the age-related effects of subfertility limit the likelihood of success. Assisted reproduction can overcome the barriers to fertility caused by tubal disease and low sperm count, but little progress has been made in reducing the effect of increasing age on ovarian function. The next 5-10 years will likely see further increases in birth rates in women with subfertility, a greater awareness of lifestyle factors and a possible refinement of current assisted reproduction techniques and the development of new ones. Such progress will bring challenging questions regarding the potential benefits and harms of treatments involving germ cell manipulation, artificial gametes, genetic screening of embryos and gene editing of embryos. We hope to see a major increase in fertility awareness, access to safe and cost-effective fertility care in low-income countries and a reduction in the current disparity of access tofertilitycare.

Human Embryo Gene Editing in China: The Uncertain Legal Status of the Embryo

In this article, we examine processes of ethical deliberation, legislative developments, and social and political factors that have contributed to the emergence of human embryo gene editing as a field of life science research in China. For this purpose, we examine conceptions of the legal status of the human embryo in three domains of China’s legal system: in patent law, in the jurisdictional domain of birth control, and in civil law. Each of these legal domains handles a different conception of the human embryo’s moral and legal status, and in all three the embryo’s status is contested and subject to changes. Our findings suggest that definitions of the legal status of the human embryo in China are at present in the midst of a renegotiation progress, which is driven by a variety of developments and causes. In this paper, we focus on three types of controversies that underlie this renegotiation process and we illustrate the conflicting aspirations, ethical arguments, and moral priorities that inform these conflicts. We end this article with three lines of consideration that might structure future studies on this issue.

One small edit for humans, one giant edit for humankind? Points and questions to consider for a responsible way forward for gene editing in humans

Gene editing, which allows for specific location(s) in the genome to be targeted and altered by deleting, adding or substituting nucleotides, is currently the subject of important academic and policy discussions. With the advent of efficient tools, such as CRISPR-Cas9, the plausibility of using gene editing safely in humans for either somatic or germ line gene editing is being considered seriously. Beyond safety issues, somatic gene editing in humans does raise ethical, legal and social issues (ELSI), however, it is suggested to be less challenging to existing ethical and legal frameworks; indeed somatic gene editing is already applied in (pre-) clinical trials. In contrast, the notion of altering the germ line or embryo such that alterations could be heritable in humans raises a large number of ELSI; it is currently debated whether it should even be allowed in the context of basic research. Even greater ELSI debates address the potential use of germ line or embryo gene editing for clinical purposes, which, at the moment is not being conducted and is prohibited in several jurisdictions. In the context of these ongoing debates surrounding gene editing, we present herein guidance to further discussion and investigation by highlighting three crucial areas that merit the most attention, time and resources at this stage in the responsible development and use of gene editing technologies: (1) conducting careful scientific research and disseminating results to build a solid evidence base; (2) conducting ethical, legal and social issues research; and (3) conducting meaningful stakeholder engagement, education and dialogue.

Kathy Niakan: at the forefront of gene editing in embryos

Kathy Niakan: at the forefront of gene editing in embryos

Research on gene editing in embryos is justified, group says

Research on gene editing in embryos is justified, group says

Responsible Use of Human Gene-Editing Technologies.

Human Gene TherapyVol. 26, No. 7 Special Issue: Focus on Genome EditingGuest Editor: Dr. Feng ZhangEditorialsResponsible Use of Human Gene-Editing TechnologiesVictor J. Dzau and Ralph J. CiceroneVictor J. DzauPresident, National Academy of Medicine.Search for more papers by this author and Ralph J. CiceronePresident, National Academy of Sciences.Search for more papers by this authorPublished Online:15 Jul 2015https://doi.org/10.1089/hum.2015.29004.vjdAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Responsible Use of Human Gene-Editing Technologies." Human Gene Therapy, 26(7), pp. 411–412FiguresReferencesRelatedDetailsCited byPosition Calibration of a Single Cell Measurement With Electrochemical Impedance SpectroscopyIEEE Sensors Journal, Vol. 23, No. 5Ethics and Genomic Editing Using the Crispr-Cas9 Technique: Challenges and Conflicts12 November 2022 | NanoEthics, Vol. 16, No. 3Application of Molecular Genetics7 October 2022The Ethics of Gene Editing from an Islamic Perspective: A Focus on the Recent Gene Editing of the Chinese Twins3 March 2020 | Science and Engineering Ethics, Vol. 26, No. 3Map of ethical conflicts of the CRISPR-Cas9 gene edition techniqueMedicina Clínica (English Edition), Vol. 153, No. 9Mapa de conflictos éticos de la técnica de edición genética CRISPR-Cas9Medicina Clínica, Vol. 153, No. 9Senior Gene Therapy Scientists Take a Stand Against Human Embryo Gene Editing Terence R. Flotte16 July 2019 | Human Gene Therapy, Vol. 30, No. 7The ethics of clinical applications of germline genome modification: a systematic review of reasons6 August 2018 | Human Reproduction, Vol. 33, No. 9Drawing the Line: Disability, Genetic Intervention and Bioethics17 July 2017 | Laws, Vol. 6, No. 3Gene Therapy and Gene Editing for the Corneal DystrophiesAsia-Pacific Journal of Ophthalmology, Vol. 5, No. 4The societal opportunities and challenges of genome editing5 November 2015 | Genome Biology, Vol. 16, No. 1 Volume 26Issue 7Jul 2015 InformationCopyright 2015, Mary Ann Liebert, Inc.To cite this article:Victor J. Dzau and Ralph J. Cicerone.Responsible Use of Human Gene-Editing Technologies.Human Gene Therapy.Jul 2015.411-412.http://doi.org/10.1089/hum.2015.29004.vjdPublished in Volume: 26 Issue 7: July 15, 2015PDF download

Targeted Germline Modifications in Rats Using CRISPR/Cas9 and Spermatogonial Stem Cells.

Organisms with targeted genomic modifications are efficiently produced by gene editing in embryos using CRISPR/Cas9 RNA-guided DNA endonuclease. Here, to facilitate germline editing in rats, we used CRISPR/Cas9 to catalyze targeted genomic mutations in rat spermatogonial stem cell cultures. CRISPR/Cas9-modified spermatogonia regenerated spermatogenesis and displayed long-term sperm-forming potential following transplantation into rat testes. Targeted germline mutations in Epsti1 and Erbb3 were vertically transmitted from recipients to exclusively generate "pure," non-mosaic mutant progeny. Epsti1 mutant rats were produced with or without genetic selection of donor spermatogonia. Monoclonal enrichment of Erbb3 null germlines unmasked recessive spermatogenesis defects in culture that were buffered in recipients, yielding mutant progeny isogenic at targeted alleles. Thus, spermatogonial gene editing with CRISPR/Cas9 provided a platform for generating targeted germline mutations in rats and for studying spermatogenesis.