Assignment 1: What is mitochondria replacement therapy?

How are
born of three parents’ babies possible using this therapy is case of a
mother carrying a defective genome?

Mitochondria replacement therapy

Mitochondria replacement therapy is a technique that involves replacing the mitochondrial

DNA of an embryo that has a risk of mitochondrial disease with healthy mitochondrial DNA
from a donor, or the “third parent.”
Mitochondria are vital for most cells of our body because they produce energy for the cell. So
mitochondrial diseases may lead to serious health problems, such as blindness, diabetes,
neurodegenerative disease, muscular dystrophy. Sometimes it may lead to death in newborns,
children and even young adults. Mitochondrial diseases can be caused by nuclear DNA
mutations, which affect mitochondrial functioning, or by mitochondrial DNA (mtDNA)
mutations. Previous technique for avoiding mtDNA mutation was embryo donation, adoption
and egg donation. But in these three techniques there are no genetic link between the children
and the social parents (eg. adoption and embryo donation) or between the children and the
social mother (eg. egg donation). Research has shown that IVF can overcome this problem by
replacing disease linked mtDNA with healthy mtDNA either before or after fertilization. By
applying this method, it is possible to avoid genetic discontinuity between children and social
parents.

How three parent babies are born?

Mitochondria are tiny disc shaped organelles whose function is to produce energy for our
bodies metabolic activities. Human egg cells contain mitochondria like most of the cells. But
sperm cells contain mitochondria only in their tails. During fertilization, only the head
portion of the sperm can enter into the egg cell and the tail portion is left behind. That’s why
children only inherit mitochondrial DNA from her mother.
But if the mother contain a defective mitochondrial DNA, it is possible that her child may
face some physical problem during or after birth which can suffer him lifetime. The
difficulties maybe blindness, muscular dystrophy and may even lead to death. So to
overcome this problem scientists have introduced mitochondria replacement therapy. In this
method, healthy mitochondrial DNA from a female donor is transplanted to the mothers egg
or zygote. So the baby contain nuclear DNA from his biological parents and contain
mitochondrial DNA from a donor parent. That is how three parent babies are born.

Techniques involved in mitochondria replacement therapy

There are two principal methods used in mitochondria replacement therapy (MRT),
pronuclear transfer and maternal spindle-chromosome transfer. There is currently introduced
a promising third method which is polar body genome transfer. But this method is currently
under development. The ultimate goal of these techniques is to transfer the genetic material
from the affected oocyte or zygote to an oocyte or zygote that contains healthy mitochondria.
This replacement will eliminate the mitochondrial mutation from the germline as it is the
independent nature of mitochondria.
a. Pronuclear transfer technique
In this method, two zygotes are raised in vitro after fertilization. Here one zygote comes
from the biological parents with pronuclei and defective mitochondria and another zygote
comes from the donor with pronuclei and healthy mitochondria. Biological parents
pronuclei are removed from the zygote and transplanted to the donors enucleated zygote
which has healthy mitochondria. The modified zygote is then transferred to the mother’s
womb.

b.

Maternal spindle transfer (MST) technique: This technique is applied before

fertilization which is a kind of selective reproduction system. In this method, biological
mothers spindle complex is removed from the defective egg at the metaphase stage. It is
then transplanted into the perivitelline space of the enucleated donor's egg which has
healthy mitochondria. The modified embryo is then transplanted into the mother’s womb.
This technique is preferable because maternal spindle contains a little amount of
cytoplasm which decreases the possibilities of mtDNA carryover and mutations.
c. Polar body genome transfer (PBT)
Polar bodies are two small bodies with unequal cytoplasm and the same number of
chromosomes equal to the primary oocyte's nucleus, formed from the mammalian oocyte
during the processes of oogenesis. The first polar body is diploid and second polar body is
haploid in nature. There are two different methods of PBT.
In first polar body transfer method, biological mother’s first polar body containing her
nuclear DNA and defective mitochondrial DNA is transferred to the donor mother’s
oocyte containing nonpathogenic mtDNA from which the nuclear DNA had been
removed. The reformed oocyte is then transplanted to the mother’s womb.
 In second polar body transfer method, both biological mother’s oocyte with defective
mtDNA and donor mother’s oocyte with healthy mtDNA is fertilized. The biological
mother’s second polar body, containing nuclear DNA and defective mtDNA is then
transferred to the zygote of donor mother containing healthy mtDNA and removed
pronuclei. The resulting embryo is then transplanted in the mother’s womb.

Conclusion

Mitochondria replacement therapy is a revolutionary treatment for the parents who have
defective mitochondrial genome. These techniques include pronuclear transfer, maternal
spindle transfer, polar body genome transfer and few more methods which are under research
and
development. Among them both pronuclear transfer and maternal spindle transfer methods
have been successful in animal and human models. Polar body genome transfer is also a
successful method but it is under development. There are many ethical issues surrounding
this therapy. For greater purpose, we should use this method ethically.

Reference

1. https://www.cell.com/heliyon/pdf/S2405-8440(20)31487-0.pdf
2. https://cdn.dal.ca/content/dam/dalhousie/pdf/sites/noveltechethics/501.pdf
3. https://pdfs.semanticscholar.org/e017/d3bdcd9ca2032570ace86cef3074b59fe140.pdf
4. https://www.fertstert.org/article/S0015-0282(13)03290-1/pdf