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Why Looking Back May Be The Way Forward

Why Looking Back May Be The Way Forward

In all walks of life, but particularly in science, we are marching inexorably forwards at a rate almost unmatched by any other point in history. Daily, research that was at one point ground-breaking is replaced by something shiny and new. This isn’t a bad thing, far from it. Indeed, it is why I find science such an exciting field to be involved in; we are constantly discovering new things and improving our understanding of the world in which we live.

One unfortunate side effect of this culture of novelty and progress is that the merits of ‘old’ research can be cast by the wayside. It is encouraging, therefore, that the solutions to some of our seemingly unsolvable problems can be found residing in the long-abandoned archives of medical research.

The best example of turning to established research to solve a persistent problem is the search for HIV therapeutics. HIV, the virus responsible for the AIDS epidemic, has proved a resilient foe for medical research to face. The search for an efficacious HIV vaccine has yielded nothing and while the therapeutics being produced are pretty good, they can always be better.

One of the key targets in the treatment of HIV is the viral protease, an enzyme that cuts up the viral pre-cursor proteins, allowing progeny virions to mature and infect further cells in an infected individual. One of the firt tasks when targeting protease was, as it often is, to determine its crystal structure. Upon doing this, it was determined that it had a similar structure to Renin, an enzyme that mediates extracellular volume and vasoconstriction, thus mediating the body’s main arterial blood pressure. Using this knowledge, the first generation of HIV protease inhibitors were based on the many Renin inhibitors that already existed, to treat hypertension.

Determining the structure of HIV protease allowed researchers to pioneer the use of Renin-like inhibitors in the treatment of HIV.
Determining the structure of HIV protease allowed researchers to pioneer the use of Renin-like inhibitors in the treatment of HIV.

While the protease inhibitors came early in the timeline of HIV research, there are a number of similar examples still at the forefront of HIV therapeutics research. One of these is the potential use of ribozymes as anti-HIV drugs. Ribozymes are RNA molecules that are capable of catalyzing specific biological reactions. Their discovery showed that RNA can act both as genetic material, like DNA, but also as enzymes, giving them a far wider range of roles than first thought. One of the main processes catalyzed by ribozymes is the cleavage and removal of exons from pre-mRNA, thus converting it into mature mRNA from which proteins can be synthesised.

In a fine example of using ingenuity to connect two seemingly unrelated subjects, there is now great excitement about the use of ribozymes to treat HIV. The basis for the hypothesis? Well, since ribozymes can cut up RNA and HIV has an RNA genome, can ribozymes be targeted against the HIV genomes, destabilising them and destroying the virus? That is precisely the thought behind a trial that is currently in Phase II testing, which uses gene therapy to introduce a gene coding for the OZ1 ribozyme. This would potentially be a one time cure and is showing good preliminary results, with viral load far lower in those that received the ribozyme.

These examples show just how important it is, despite the exciting times in which we are working, to remain aware of the work that has been done before. A new development in a field doesn’t always have to mean a brand new product. With the wealth of knowledge that the science community has already accumulated, we could well be sitting on a gold-mine of potential solutions to the problems posed by our most fiendish foes.

‘Til Next Time…

Joe

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