This week’s paper describes
a new technique that could be used to manipulate human oocytes (i.e. eggs) to
prevent a group of diseases called mitochondrial diseases. The paper was presented by Tachibana et al. in Nature along with a similar paper by Paull et al. For the sake of brevity, I will only discuss
the findings from the first paper.
Mitochondria
So what are mitochondria? Mitochondria are little compartments in the
cell that make cellular energy. They
convert the energy stored in food into an energy source that the cell can use
to drive chemical reactions. In other
words, they are absolutely essential for our survival. The oxygen that we breathe in goes to the
mitochondria to aid in this energy conversion, and we all know how vital oxygen
is.
There are two other
interesting facts about mitochondria that relate to our story:
1) All the mitochondria in
our body are duplicates of the mitochondria that were in our mother’s egg. In other words, embryonic mitochondria are
not made from our genomic DNA (gDNA) or from sperm contributions.
2) Mitochondria have their
own DNA , which directs the synthesis of proteins that are necessary for their
function. This DNA is known as
mitochondrial DNA (mtDNA) and it is only inherited from the mother, since all
mitochondria originate from the egg.
If there are mutations in
the mtDNA, then this can lead to problems with the synthesis of cellular
energy, which can lead to human diseases known as mitochondrial diseases. There are different types of mutations, which
can affect people in different ways and with differing severities. In this paper, the authors propose a way to
prevent mitochondrial diseases from being inherited from generation to
generation. Let’s see how that works.
Nuclear transplantation
Let’s say you have a female
patient with a mitochondrial disease, who wants to have a healthy child. She is guaranteed to pass this disease on to
her child via the mitochondria in her oocytes.
However, most of what makes the child “hers” is what lies in the mother’s
genomic DNA, not in the mitochondrial DNA.
What if you could take the mother’s genomic DNA (plus the DNA from the
father) and stick it into a healthy “enucleated” oocyte from a donor who has
good, functioning mitochondria? All the
genomic DNA will have to be cleared out of the donated oocyte first, creating
an enucleated egg. The embryo that
results from this nuclear transplantation will have genomic DNA from its mother
and father, but its mitochondria will originate from the donor oocyte. This would circumvent the mutated mtDNA that
is in the real mother’s oocyte.
Tachibana et al. obtained
human oocytes from volunteers and transfered the genomic DNA from one into
another. They then injected these
oocytes with sperm DNA (like during real fertilization) and observed what
happened. Some oocytes failed to be
fertilized and others died soon after, but a handful of oocytes survived into
the blastula stage of development. You
can’t really grow a human embryo in a dish beyond the blastula stage and they
are not allowed (yet) to implant these into women, so we don’t know what would
happen to a child born from this procedure.
They did carry out the above
scenario with monkeys. They transplanted
the genomic DNA from one oocyte into another and implanted the blastula into
another female monkey who carried the embryo to term. The monkey youths are 3 years old now and
doing just fine. Their maternal genomic
DNA is from one mother and their mitochondria are from a different oocyte
donor.
Isn’t this amazing? I seriously doubt this procedure will be
approved for human use anytime soon, because it’s too much like cloning, which
basically follows the same procedure of putting genomic DNA into an enucleated
egg. It's a cool idea, though.
