YouTube Transcript:
Gene Therapy

It’s professor Dave, let’s get therapeutic.
When we introduced some concepts in biotechnology, we briefly mentioned the notion of gene therapy,
and alluded to its enormous potential for treating genetic disorders.
This is a fascinating and promising area of study, so in order to better understand it,
let’s take a closer look now.
There are a number of disorders that can be traced to a single defective gene.
Some mutation has arisen, which alters the product of gene expression, and the resulting
protein does not perform its function as intended, which creates problems for that cell, and
by extension, the organism.
But what if we could fix this gene?
What if a normal allele could take the place of this defective one?
That would necessarily solve the problem for that cell, and if this could somehow be done
for every cell that possesses the mutation, it would solve the problem for the organism,
definitively curing the disease.
That is precisely what gene therapy seeks to do.
Take for example a type of severe combined immunodeficiency that causes bone marrow cells
to be unable to produce a vital enzyme, an issue which stems from single gene.
Because bone marrow cells include stem cells that give rise to all the cells in the blood
and immune system, this can be a huge problem.
A solution to this is as follows.
We can synthesize an RNA version of the normal allele for the gene of interest, and insert
it into a retrovirus.
Recall from our study of viruses that a retrovirus has the ability to generate a DNA transcript
of its RNA genome, which it then inserts into a host cell for replication.
We then allow this retrovirus, containing our cloned gene, to infect bone marrow cells
that have been removed from the patient.
The virus is taken into these cells, and viral DNA, containing the normal version of the
gene of interest, is inserted into the genome.
These recombinant cells are then injected back into the bone marrow of the patient,
and as these continually divide over an extended period of time, as bone marrow cells do, more
and more cells have the capacity to produce the vital enzyme, and the disorder is alleviated.
So as we just discussed, gene therapy can involve inserting a normal allele into a genome
to compensate for the activity of a mutated gene.
It can also involve introducing a completely novel gene into an organism.
It can even involve inactivating, or knocking out a mutated gene, so that it will not be
expressed.
In addition, the novel DNA is not always delivered by a virus.
There are techniques that involve the introduction of foreign genes into cells by electroporation.
This is where an electrical field is used to increase the permeability of the cell membrane,
so that the DNA can pass through tiny temporary holes.
DNA can even be injected into cells with incredibly thin needles.
There have been some complications with gene therapy, largely due to the uncertainty associated
with where the insertion of the retroviral vector will occur on the genome.
It is also difficult to control the manner in which this new gene is expressed.
However, there is still cause for cautious optimism, as a number of very serious genetic
diseases have been treated with significant success, and this is an area of ongoing study.
There are those that cite ethical concerns with this kind of practice, in addition to
the obvious technical challenges.
Is it appropriate to modify the genome of a living human?
Well it is worth noting that this has already been done through blood donation and organ
transplantation.
These both introduce living cells with foreign DNA into someone’s body.
Is gene therapy really that different?
Of course one could argue that it is a slippery slope.
Will this technology be used to genetically engineer humans, and if so, according to what
guidelines?
This type of thought could lead to the practice of eugenics, whereby efforts are made to control
the genomes of a population.
This has been disastrous in the past, and under the wrong political influence, could
be disastrous in the future.
But just as with the dangers brought on by cars, airplanes, and the internet, we must
balance a zeal for progress with extreme caution.
Most importantly, while certain concepts seem like science fiction, we must consider them
seriously while they still feel that way, so that we have a firm idea of what to do
when they eventually become a reality.