Gene therapy or living drugs is one of the most exciting areas of biotechnology, and we’d like to tell you about some of the progress we’ve made in expanding the potential use of gene therapy.

But first, why are we talking about gene therapy can enable the treatment of some of the big blights on human health cancer, genetic disorders and infectious diseases. It does this by correcting or inserting a gene instead of using drugs or surgery. In collaboration with the Children Medical Research Institute (CMRI), we are working on improving gene therapy vector technologies.

Around since the early 1970s, gene therapy, provides a one-time treatment option by rewriting or fixing errors in the natural genetic code. Scientists are keen to know how to better optimise delivery of gene therapy machinery into cells.

Current delivery vehicles or “vectors” are mostly plasmids, nanostructures or viruses. Viruses are the most investigated method due to their excellent capability to invade cells and insert their genetic material. Among viral vectors, adeno-associated viruses (AAV) are the most used carriers for delivering DNA due to their versatility and safety. Over the last four decades, viral vectors have been progressively modified to increase their delivery of therapeutic content in a safely and effectively. These optimised AAV vectors are used in the treatment of genetic disorders, such as Leber’s congenital amaurosis and for spinal muscular atrophy. Yet, this technology is limited as the maximal size of the therapeutical cargo is 4.3kb. This restricts the number of human diseases that can be treated with these approaches.

Another problem is that gene therapy is the most expensive drug on the planet. Costs per treatment ranging from $425,000 per eye for Luxturna, to $2.1 million per patient for Zolgensma. Understandably they are often delivered in a one-off treatment and the drug-development and manufacturing cost can be shared only by a small number of people suffering from the rare genetic diseases they are targeting.

Despite the cost, gene therapy promises life-changing treatments for the 400 million people worldwide affected by rare genetic diseases. In the future, gene therapies might even be applied to a wider range of indications with genetic susceptibility, such as heart disease and chronic pain.

Figure 1: Schematic showing the process of gene therapy. Figure from the US Food and Drug Administration

Incrasing the DNA cargo to unlock the therapeutic horizon

This is where bioinformatics enters the stage. We want to find a way to reduce the space or volume occupied by the viral genome using cutting edge compute resources and advanced bioinformatics approaches. This will allow longer genomes to be packed so more diseases can be tackled.

Figure 2: Schematic showing AAV capsid and its vector structure employed in gene therapy. Figure from Tretiakova et al. 2018

Opening gene therapy access to a larger population

Increasing packaging capacity will not only enable the therapeutical access to a wider range of conditions but will also improve vector manufacturing and lower cost of therapy.

One of the new projects in precision medicine at AEHRC is promising us some excited outcomes!

There’s so much potential in this space to make a difference to health in precise, informed and cost-effective ways. Stay tuned for more on Anne’s project.