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Should Genome Editing Replace Embryo Selection Following PGT?
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
For the last 30 years, carriers of disease-causing mutations wishing to increase their chances of having unaffected, genetically related children, have needed to seek PGT or prenatal diagnosis. More recently, advances in genome engineering technologies have begun to suggest that other approaches, involving germline genome editing (GE), might represent feasible alternatives. While heritable genome editing does not currently exist as a widely available, validated reproductive strategy, it could do so in the future. In theory, the application of GE for the avoidance of inherited disease could allow the modification of a mutant gene in order to restore a wild-type DNA sequence. Such an approach would shift the paradigm of current reproductive strategies away from the diagnosis and exclusion and towards “cure” (18).
Genome-Editing Strategy for Medicinal Plants Growing under Adverse Environmental Pollution
Published in Azamal Husen, Environmental Pollution and Medicinal Plants, 2022
Enhanced expression of enzymes such as metallothionein, metal reductions etc., and the pathways of pollution transport (vacuolar compartmentation of heavy metals or the transport of pollutants to the rhizosphere) are the primary targets of phytoremediation. The low efficiency of Cas9 gRNA-mediated cloning for enhancing phytoremediation has been carried out in some selected plants only (Belhaj et al. 2015). Scientists suggested the use of an all-in-one plasmid approach by amalgamating diverse gRNAs with Cas9 in a single T-DNA to improve the editing (Mikami et al. 2015; Bortesi and Fischer 2015). Due to the complex nature of plant genomes, it is very difficult to manage site-specific mutagenesis in plants and therefore Cas9 gRNA could be wondrous in facilitating the targeting of multiple sequences and traits simultaneously. CRISPR-aided genome engineering has great potential for exploiting plant genomes for enhancing phytoremediation.
Reproductive Approaches to Prevent the Transmission of Mitochondrial Diseases
Published in Sara C. Zapico, Mechanisms Linking Aging, Diseases and Biological Age Estimation, 2017
María Jesús Sánchez-Calabuig, Noelia Fonseca Balvís, Serafín Pérez-Cerezales, Pablo Bermejo-Álvarez
Both oocyte transplantation and nuclear genome transfer results in an embryo carrying genetic material from three different donors, which raises biological, medical and ethical concerns (Hayden 2013, Reinhardt et al. 2013). In contrast to these techniques, selective elimination of mutant mtDNA does not introduce any exogenous genetic material: it only reduces the load of mutant mtDNA. The reduction is achieved by using site-specific endonucleases: Zinc Finger Nucleases (ZFN), Transcription Activator-like Effector Nucelases (TALEN) or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR). These three genome engineering systems are able to find specific loci across the genome and induce a Double-strand breaks (DSB) close to their target site. DSB in chromosomes is repaired by NHEJ or, less frequently, by HR. As NHEJ, the most frequent repair mechanism, is an error-prone mechanism, it often results in point mutations, which may alter the open reading frame of a particular gene. These systems have revolutionized the transgenesis field by allowing the efficient and easy-to-tailor mean (especially CRISPR) to generate knock-outs (Shen et al. 2013, Wang et al. 2013). However, in contrast to chromosomic DNA, DSB in mtDNA are usually not repaired by NHEJ or HR and, therefore, DSB often results in mtDNA degradation (Shokolenko et al. 2013). Therefore, elimination of mutant mtDNA molecules can be achieved by directing site-specific endonucleases against the mutant sequence.
Personhood, Welfare, and Enhancement
Published in The American Journal of Bioethics, 2022
That being said, genetic enhancement, as it is currently implemented, is not person-effecting. Phrases such as “knocking out a gene” are misleading in this regard, since they suggest that genetic enhancement is akin to pressing a particular switch in the internal mechanisms of a person’s body. The science is much more complicated than that, as Sparrow emphasizes. The latest genome engineering technologies (CRISPR-Cas) merely affect the probabilities of how an embryo will develop. From the perspective of philosophy of science, this is not surprising: cells are highly stochastic and the common textbook representation of them as complex machines is a significant idealization of reality (Nicholson 2019). For many epistemic challenges this idealization does the job, but for others it does not and the ethics of CRISPR-Cas seems to be one of those. Whether following the technique of editing the genome of a live embryo, or of inducing gametogenesis of gene-edited pluripotent stem cells, it is necessary to conduct several attempts and subsequently select the most desirable embryo. In other words, genetic enhancement for the foreseeable future will involve generating and selecting between multiple embryos. Instead of increasing the welfare of existing persons, genetic enhancement de facto selects which persons can come into existence.
Dynamic Aspects of Human Genetics: Is the Human Germline the Bioethical Key to Human Genetic Engineering?
Published in The American Journal of Bioethics, 2022
We are certainly in need of a more comprehensive view of our biology and in light of that view, of a more sophisticated way to adjudicate our moral concerns with bioengineering ourselves. And, the way in which we think about the human microbiome will most certainly impact all the ways in which we think about the dynamic of human genetics, the nature of certain genetic interventions, and ultimately, the values that guide this enterprise. The idea that the human germline provides the ultimate reality that we should not alter is at best a normative chimera. Again, this is not to say that changes in one’s germline (host + microbiome) cannot drastically impact one’s welfare or potentially future generations. But, in addition to continuous mutations in the human genome, a comprehensive view of human heritability serves as a reminder (as Lewens (2020) has already shown for epigenetic inheritance) that bioethical conversations about human genome engineering can no longer overlook the complexity of our biology for the sake of conserving a fictitiously unchanging part of our biochemistry.
Application in Gene Editing in Ovarian Cancer Therapy
Published in Cancer Investigation, 2022
Shuang Luo, Yujiao Wang, Yongyu Tao, Shuo Li, Zirui Wang, Wei He, Hangxing Wang, Nan Wang, Jianwei Xu, Hailiang Song
Gene editing, also known as genome editing or genome engineering, is a new and accurate genetic engineering technology that can be used to modify specific target genes. The technique relies on genetically engineered nucleases (also known as “molecular scissors”) that cut double-stranded DNA at specific loci in the genome and induce the repair of these breaks through non-homologous terminal connections or homologous recombination, finally leading to targeted mutations. Based on this characteristic, nucleases can efficiently carry out site-directed gene editing. At present, the technique is used in a variety of clinical fields, such as gender identification, and is also a promising strategy for OC therapy. Its ability to specifically knockout genes, promote or silence gene expression, can be used to alter the high expression of oncogenes and the low expression of tumor suppressor genes in OC, so it can be used as a new therapeutic approach. Although the status of gene editing has been greatly improved, gene editing still faces great challenges in ovarian cancer: first, how to accurately locate ovarian cancer-related genes; second, how to ensure the efficacy and safety of patients after gene therapy, and last but not least, how to promote the use of gene therapy for ovarian cancer in clinical practice. This review summarizes the application of gene editing in the treatment of OC and the underlying mechanisms, in order to stimulate its use in the clinic and improve the survival rate and quality of life of OC patients.