This proposal aims at the (pre-)clinical validation of the novel Nuclear Transfer (NT) technology in
assisted reproductive technology for two specific indications, being (1) female-related infertility and
(2) mitochondrial DNA (mtDNA) diseases. The NT technology involves the transfer of the nuclear
genome from a patient’s diseased or inferior quality oocyte or zygote to a healthy donor counterpart
from which the nuclear genome was removed. The resulting NT embryos contain the nuclear DNA
from both prospective parents and the cytoplasm, including the mtDNA, originating from the donor

This technology has already shown potential in overcoming transmission of mtDNA diseases, mostly
in a research setting, as to date only one baby was born after NT to overcome transmission.
More recently, the NT technology has also been proposed to overcome specific female-related
infertility indications that could be attributed to inferior oocyte quality, for which generally oocyte
donation is advised. NT could provide these patients still a chance to obtain their own genetic child.
Both experimental evidence on animal and human models as well just recently published clinical data
on a limited number of patients support the feasibility of this approach.
The currently available (pre-)clinical data is however still insufficient to fully support clinical
implementation of the technique, especially to overcome mtDNA disorders, because some of the
mutant mtDNA which is still transferred with the nucleus, can take it over from the healthy donor
mtDNA during life. As such, we first want to further validate the NT technology for specific infertility
disorders (failed fertilization and embryo developmental arrest) in a pre-clinical context, by extensive
-omics analyses on the created NT embryos; and compare different NT strategies in patients with
mtDNA diseases. Thereafter, NT will be clinically implemented, first for infertility, secondly for
mitochondrial diseases.