Here is a copy of the article I did for the Spring Edition of The Walton. You can read more here.
Over the past year in Ireland, there has been much excitement
with regards to gene therapy, with a couple of potentially ground-breaking
developments occurring. So let’s pause and look at what gene therapy is, how it
is currently being used and perhaps look towards the future.
Gene Therapy is an umbrella term for many types of
treatments. Ultimately it involves changing, fixing or replacing genes that are
defective or mutated in someone’s cell such that the cells can function again. Remember
that genes represent the code by which just about everything that happens in
the body follows; an instruction manual for all the processes of the body. So if
some of that code is missing, or incorrect, the body functions won’t work
properly. Examples of such diseases would be cystic fibrosis, Huntington’s
disease, Sickle-cell anaemia and a huge range of immunity disorders. Even cancer
is caused by genetic mutations. So if there was a way to fix the code, repair
it in some way, this would have huge benefits to thousands of people.
One way to fix a broken code involves using viruses. This may
sound alarming, but it is actually quite effectively used. The basic principal
revolves around using a harmless virus i.e. one that will only infect certain
cells and won’t replicate, to carry the corrected gene code to cells. Viruses
do this anyway – when they infect a person, they are often actually infecting
the cells, their own gene codes being incorporated into the host cell. Usually
this is extremely detrimental, and cell death ensues, but by controlling what
gene sequences are included in the virus, you can potentially tailor what
happens when a virus infects a cell.
The diagram shown here shows a virus (called a vector because
it is basically a transport vehicle) attaching to a cell. It is an adenovirus
vector. Adenovirus is associated with respiratory, intestinal, and eye
infections in humans (especially the common cold). As shown in the diagram, the
virus is taken into the cell and then travels to the nucleus (the pink thing).
It attaches to the surface of the nucleus and injects the DNA into to core of
the nucleus. Remember that the nucleus of the cell is where we hold all our own
genetic material.
The DNA type molecule in this case isn’t a double-stranded
molecule, but instead is a single strand, and can thus be read by the cells
replication molecules. These molecules are called messenger RNA, and they are
part of the process by which new proteins are formed. Thus, if the correct DNA
is present, the correct proteins will be made, and so any dysfunction that
occurred before may be rectified.
There are two methods to introduce the genetic material into
the patient. Ex vivo gene therapy involves removing cells from an individual’s
body, modifying them to include the correct genetic material using a vector,
and then transferring these cells back into the patient’s body. In Vivo gene
therapy involves injecting the viral vector directly into the patient, in the
hopes that the virus with infect and ‘fix’ the damaged cells. Both methods have
seen varying levels of success.
Cystic fibrosis is a genetic disease which is particularly common
in Ireland and results in a build-up of mucous in the lungs of affected
individuals. Vital research in University College Cork is currently underway to
cure cystic fibrosis. The central tenet to this research involves creating
breaks in both strands of the DNA at targeted sites. This process is enabled by
the use of Zinc-finger nucleases which are specially designed DNA-binding proteins,
with high specificity.
By intentionally creating a break in the DNA strands, you
can induce homologous recombination (a time of genetic repair) between the
broken strands. This can allow you to include the correct sequence in the
genome at that point. More in-depth analysis of the current status of research,
both here and in the UK will be presented in next issue of Walton Magazine.
Similarly, a novel treatment for bacterial infection of Pseudomonas
aeruginosa in cystic fibrosis patients is also seeing some success, also using
gene therapy. The research was carried out the Alimentary Pharmabiotic Centre
[APC], a Science Foundation Ireland funded research centre based in UCC, Teagasc
Moorepark Research Centre and CIT.
The researchers, led by Professor Colin Hill in UCC and
Professor Paul Ross in Teagasc, took advantage of a method called phage
therapy. This involves identifying and characterising bacterial viruses which
can attack and kill Pseudomonas aeruginosa within minutes of initial contact.
One of the advantages of phage therapy is that any viruses which ‘find’ a
target multiply at the target site, generating more viruses and amplifying the
therapeutic effect. This research is paving the way for the development of new
treatments for Pseudomonas infections in cystic fibrosis patients.
So with two keen and different ways of tackling the disease,
either by treating the infections that occur or by curing the disease itself,
it goes without saying that there is bound to be some new revelation this year.
We have barely scratched the iceberg in this article with all research for
other diseases that could be treated, so maybe that’s for the next time!
