Ooplasmic and nuclear transfer to prevent mitochondrial DNA disorders: conceptual and normative issues

Bredenoord, Annelien L.; Pennings, Guido; Wert, Guido de

doi:10.1093/humupd/dmn035

Cited by 58 publications

(74 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, the cell to be transferred in embryo cloning originates from an embryo. [15] The latter implies that the [16] summarised these regulatory approaches from 16 countries. Cloning concerns are especially applicable to the blastomere nuclear transfer technique, where a blastomere is derived from an embryo that consists of several cells, not just a single cell as found during transfer of spindles or pronuclei (Fig.…”

Section: Alteration Of Germ Line Geneticsmentioning

confidence: 99%

Mitochondrial transfer: Ethical, legal and social implications in assisted reproduction

2015

View full text Add to dashboard Cite

Section: Alteration Of Germ Line Geneticsmentioning

confidence: 99%

Mitochondrial transfer: Ethical, legal and social implications in assisted reproduction

2015

View full text Add to dashboard Cite

“…According to germline therapy nuclear transfer technology aims to remove mitochondria carrying mutant mtDNA from maternal oocytes and replace them with normal mitochondria from a healthy donor's ooplasm (ooplasmic transfer) (61,62). Such innovative technologies may be useful in the near future to prevent transmission of mtDNA disorders at the preconception or conception stage.…”

Section: Mitochondrial Medicinementioning

confidence: 99%

Transduction of Human Recombinant Proteins into Mitochondria as a Protein Therapeutic Approach for Mitochondrial Disorders

Papadopoulou

Tsiftsoglou

2011

Pharm Res

View full text Add to dashboard Cite

Protein therapy is considered an alternative approach to gene therapy for treatment of genetic-metabolic disorders. Human protein therapeutics (PTs), developed via recombinant DNA technology and used for the treatment of these illnesses, act upon membrane-bound receptors to achieve their pharmacological response. On the contrary, proteins that normally act inside the cells cannot be developed as PTs in the conventional way, since they are not able to "cross" the plasma membrane. Furthermore, in mitochondrial disorders, attributed either to depleted or malfunctioned mitochondrial proteins, PTs should also have to reach the subcellular mitochondria to exert their therapeutic potential. Nowadays, there is no effective therapy for mitochondrial disorders. The development of PTs, however, via the Protein Transduction Domain (PTD) technology offered new opportunities for the deliberate delivery of human recombinant proteins inside eukaryotic subcellular organelles. To this end, mitochondrial disorders could be clinically encountered with the delivery of human mitochondrial proteins (engineered via recombinant DNA and PTD technologies) at specific intramitochondrial sites to exert their function. Overall, PTD-mediated Protein Replacement Therapy emerges as a suitable model system for the therapeutic approach for mitochondrial disorders.

show abstract

“…To avoid this complication, the recipient oocytes could be parthenogenetically activated, then enucleated and used as recipient cytoplasts. Alternatively, zygotes that have been abnormally fertilized (mono, tripronuclear) could also be used as recipient cytoplasts [20]. The question that remains is whether they will be available when the patient embryo needs to be manipulated.…”

Section: Transfer Of Pronucleimentioning

confidence: 99%

“…Thus, unlike the above-discussed experimental schemes, this approach cannot be used for elimination of mutated mitochondrial DNA, but it can supply the embryo with some essential organelles (including mitochondria) and molecules that are necessary for driving early embryonic development. As an increased frequency of certain abnormalities has been detected after birth in children, the use of this technique has been questioned, and it is not commonly used at present [20].…”

Section: Cytoplasmic Transfermentioning

confidence: 99%

How to Repair the Oocyte and Zygote?

Fulka

Langerova

Barnetova

et al. 2009

Journal of Reproduction and Development

View full text Add to dashboard Cite

Abstract. The supply of human oocytes is very limited. This restricts not only certain assisted reproduction procedures in IVF clinics where recipients wait for oocytes from donors, but also development of some promising approaches, like therapeutic nuclear transfer with subsequent derivation of patient compatible embryonic stem cells. Moreover, in some patients, collected oocytes exhibit certain specific defects, and logically, we can expect that after fertilization, the embryos arising from these defective oocytes may not develop or that their development might eventually be compromised. For this reason, an increased effort to determine how to repair oocytes is evident in the literature. In general, abnormalities (defects) can be detected in different oocyte components, the zona pellucida, cytoplasm, nucleus (chromosomes) and nucleolus. Whereas defects of a nuclear component are impossible (nuclear DNA) or very hard to repair (nucleolus), zona pellucida abnormalities and cytoplasm defects (for example, if containing mutated mitochondrial DNA, mtDNA) can be repaired in some cases with the help of micromanipulation schemes. In the present article, we will briefly outline the current methodological approaches that can be used to repair the oocyte or one-cell stage embryo. Oocytes and one-cell stage embryos are most commonly used in model animal experiments and are also considered to be the most convenient biological material for relevant therapies in humans. The reason for this is their large size (in mammals, typically about 100 μm) and the relative ease of access to this material. The important aspect is that if the oocyte or one-cell stage embryo is repaired, the resulting cell will be, in theory, normal. This will not be the case, if for example, two-cell stage embryos are manipulated. In this case, both blastomeres must be manipulated to obtain a normal embryo. Logically, this is more complicated from a technical point of view, and thus this approach is not used.The oocytes can be collected either as immature with a prominent nucleus containing one or more nucleoli (germinal vesicle, GV), maturing (with condensed chromosomes, metaphase I, anaphase I or telophase I) or mature (metaphase II). Oocytes are enclosed with a glycoprotein coat known as the zona pellucida. Here, we speculate that only so-called fully-grown oocytes can be used for manipulations because only these cells are able to undergo germinal vesicle breakdown (GVBD) and reach metaphase II (MII) stage. Less advanced oocytes (growing) do not normally undergo GVBD in culture, and if they do, they only reach the metaphase I (MI) stage [1]. Because, mature (metaphase II) oocytes are almost exclusively collected from ovaries in human assisted reproduction, one may expect that this stage would be most commonly used for manipulations. Moreover, use of these oocytes is also advantageous because they are fully developmentally competent due to maturation in their natural environment, follicles. It is well documented that developmental competence decreases ...

show abstract

Ooplasmic and nuclear transfer to prevent mitochondrial DNA disorders: conceptual and normative issues

Abstract: Further interdisciplinary debate and research is needed to determine whether a clinical application of OT and NT can be morally justified, and if so, under which conditions.

Cited by 58 publications

References 58 publications

Mitochondrial transfer: Ethical, legal and social implications in assisted reproduction

Mitochondrial transfer: Ethical, legal and social implications in assisted reproduction

Transduction of Human Recombinant Proteins into Mitochondria as a Protein Therapeutic Approach for Mitochondrial Disorders

How to Repair the Oocyte and Zygote?

Contact Info

Product

Resources

About