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Report provided to the Human Fertilisation and Embryology Authority, April 2011 - page 16 / 45

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      • 4.1.3

        Although similar methodology is employed, it is important to stress that neither MST nor PNT is equivalent to reproductive cloning (somatic cell nuclear transfer, or SCNT). Any children resulting from MST or PNT would have arisen from fertilisation and be genetically unique. They would be the genetic child of the woman receiving treatment and her partner. MST and PNT do not involve reprogramming cells or nuclei as SCNT does, which is a relatively inefficient process and associated with significant risks of abnormal development12.

    • 4.2

      Effectiveness of MST and PNT

      • 4.2.1

        There have been many experiments conducted using MST and particularly PNT in animals. PNT has been carried out since the mid 1980s in mice. All the available evidence suggests that it is very efficient and reproducible when conducted with normally-fertilised zygotes, giving rates of normal development and offspring similar to those obtained with unmanipulated zygotes. MST has also been conducted as a control in some SCNT experiments in a wide range of animals, and again the evidence suggests that it is reasonably efficient.

      • 4.2.2

        Several proof of principle studies with respect to the possible use of MST and PNT methods for treating mitochondrial disease have been carried out using animal models, including mice and rhesus macaque monkeys, and with human oocytes and abnormal human zygotes. With the exception of one mouse study13 these have not involved abnormal mitochondria; instead, researchers have used substrains or subspecies, or relied on the presence of different mtDNA haplogroups, so that sequence differences in

12 The panel examined substantial evidence about SCNT, including studies on heteroplasmy where mitochondria in the somatic cell persisted, at sometimes high levels, in the cloned embryo and offspring. This was usually associated with fusion of the somatic cell with an enucleated oocyte. This can introduce significant numbers of mitochondria that are in an active and replicating state, together with associated mitochondrial replication factors made by the somatic cell nucleus. In contrast, these factors are probably absent in mitochondria in mature o o c y t e s o r z y g o t e s , a s t h e s e m i t o c h o n d r i a d o n o t r e p l i c a t e u n t i l l a t e r . M S T a n d P N T d o n o t i n v o l v e s o m a t i c c e l l s . 1 3 Sato A., T. Kono, et al. (2005). “Gene therapy for progeny for mito-mice carrying pathogenic mtDNA by nuclear transplantation.” PNAS 102: 16765-16770. The study made use of a strain of mouse carrying mitochondria with a mtDNA deletion. They used PNT and showed that they could transfer PN from affected zygotes with minimal transfer of abnormal mtDNA and rescue the resulting offspring from defects in OxPhos.

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