Ethics and regulatory considerations for the clinical translation of somatic cell human epigenetic editing

Zeps, Nikolajs; Lysaght, Tamra; Chadwick, Ruth; Erler, Alexandre; Foo, Roger Sik‐Yin; Giordano, Simona; Lai, Poh San; Schaefer, G. Owen; Xafis, Vicki; Chew, Wei Leong; Sugarman, Jeremy

doi:10.1016/j.stemcr.2021.06.004

Cited by 8 publications

(8 citation statements)

References 10 publications

(12 reference statements)

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“…Another challenge will be the turn-around time in which all required tools for the epigenenome editing can be prepared and applied. In a wider perspective on the healthcare system, questions of costs, reimbursement, and ethical considerations also have to be kept in mind if genome editing is applied in treating human beings [ 92 , 93 ].…”

Section: Epigenetic Therapy By Genome Editingmentioning

confidence: 99%

Epigenetic Therapies in Triple-Negative Breast Cancer: Concepts, Visions, and Challenges

Lehmann

2024

Cancers

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Breast cancer, the most frequent malignancy in women worldwide, is a molecularly and clinically very heterogeneous disease. Triple-negative breast cancer is defined by the absence of hormone receptor and growth factor receptor ERBB2/HER2 expression. It is characterized by a more aggressive course of disease and a shortage of effective therapeutic approaches. Hallmarks of cancer cells are not only genetic alterations, but also epigenetic aberrations. The most studied and best understood alterations are methylation of the DNA base cytosine and the covalent modification of histone proteins. The reversibility of these covalent modifications make them attractive targets for therapeutic intervention, as documented in numerous ongoing clinical trials. Epidrugs, targeting DNA methylation and histone modifications, might offer attractive new options in treating triple-negative breast cancer. Currently, the most promising options are combination therapies in which the epidrug increases the efficiency of immuncheckpoint inhibitors. This review focusses exclusively on DNA methylation and histone modifications. In reviewing the knowledge about epigenetic therapies in breast cancer, and especially triple-negative breast cancer, the focus is on explaining concepts and raising awareness of what is not yet known and what has to be clarified in the future.

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Section: Epigenetic Therapy By Genome Editingmentioning

confidence: 99%

Epigenetic Therapies in Triple-Negative Breast Cancer: Concepts, Visions, and Challenges

Lehmann

2024

Cancers

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“…Furthermore, problems associated with the cytotoxicity and the immunogenicity of the editing tools or with the viral vectors that are used for the transfer of the editing tools 8 are avoided if an ex vivo editing approach is chosen, both in EE and GE. 7 44–46 …”

Section: Comparative Assessment Of Risks Associated With Ee and Gementioning

confidence: 99%

“… 65 16 Although there is much speaking against epigenetic inheritance in humans and the scientific discussion is controversial, the unproven assumption of epigenetic inheritance in humans has a major influence on the ethical debate about epigenetics, and on the debate about GE, 66 67 and even on the debate about EE. 7 (p. 1652)…”

Section: Comparative Assessment Of Risks Associated With Ee and Gementioning

confidence: 99%

“…The ethical discourse on the permissibility of gene therapy has increased significantly in the past decades, particularly around the Asilomar conference in 1975, 2 34 with debates exploding following the development of CRISPR/Cas for more effective and more efficient gene editing in 2012. 35–37 EE, on the contrary, has given rise to only a few ethical commentaries, 8 38 opinion papers, 7 a review incorporating ethical aspects 9 and regulatory considerations. 6 39 40 These contributions focus on EE for purposes of athletic enhancement, 6 7 on the merely hypothetical application of EE on germline cells 38 and on evaluating ethical-epistemic challenges associated with EE.…”

Section: Introductionmentioning

confidence: 99%

“…EE will not generate effects that can be passed on to descendants of edited individuals, which is a problem associated with germline GE, and a problem that can result as an unintended effect when somatic GE is used. 7 6 This would mean a reduction of unintended effects for the offspring of edited individuals.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative ethical evaluation of epigenome editing and genome editing in medicine: first steps and future directions

Alex,

Winkler

2023

J Med Ethics

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Targeted modifications of the human epigenome, epigenome editing (EE), are around the corner. For EE, techniques similar to genome editing (GE) techniques are used. While in GE the genetic information is changed by directly modifying DNA, intervening in the epigenome requires modifying the configuration of DNA, for example, how it is folded. This does not come with alterations in the base sequence (‘genetic code’). To date, there is almost no ethical debate about EE, whereas the discussions about GE are voluminous. Our article introduces EE into bioethics by translating knowledge from science to ethics and by comparing the risks of EE with those of GE. We, first (I), make the case that a broader ethical debate on EE is due, provide scientific background on EE, compile potential use-cases and recap previous debates. We then (II) compare EE and GE and suggest that the severity of risks of novel gene technologies depends on three factors: (i) the choice of an ex vivo versus an in vivo editing approach, (ii) the time of intervention and intervention windows and (iii) the targeted diseases. Moreover, we show why germline EE is not effective and reject the position of strong epigenetic determinism. We conclude that EE is not always ethically preferable to GE in terms of risks, and end with suggestions for next steps in the current ethical debate on EE by briefly introducing ethical challenges of new areas of preventive applications of EE (III).

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Is epigenome editing non-inheritable? Implications for ethics and the regulation of human applications

Sasaki-Honda,

Akatsuka,

Sawai

2023

Stem Cell Reports

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Ethics and regulatory considerations for the clinical translation of somatic cell human epigenetic editing

Cited by 8 publications

References 10 publications

Epigenetic Therapies in Triple-Negative Breast Cancer: Concepts, Visions, and Challenges

Epigenetic Therapies in Triple-Negative Breast Cancer: Concepts, Visions, and Challenges

Comparative ethical evaluation of epigenome editing and genome editing in medicine: first steps and future directions

Is epigenome editing non-inheritable? Implications for ethics and the regulation of human applications

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