Rare Genetic Diseases:
According to the World Health Organisation, approximately 400 million people are living with a rare genetic diseases worldwide. This exceeds the number of people suffering from cancer, which amounts to 43.8 million individuals, and approaches the number of people suffering from diabetes, which reaches 415 million individuals. Evidently, rare genetic diseases are not so rare. However, treatments for them are. Although approximately 6,000 rare genetic disorders will affect 1 out of every 15 persons worldwide, only 1% of these diseases has an available treatment. We at KCL iGEM have a strong dedication to medical innovation, and want to see the number availability of treatments for all rare genetic diseases rise to 100%. This is why we looked to gene therapy.
Gene Therapy: A solution?
Gene therapy provides a plausible curative solution for all rare genetic diseases. This is because 80% of rare genetic diseases are monogenic, or caused by an issue in only one gene. Gene therapy works by bringing healthy genes using vectors into cells to compensate for the unhealthy one. Thus, it would be possible to use this method of treatment for the majority of rare genetic diseases. This isn’t a revolutionary concept, as this therapy was originally developed for monogenic disorders. A significant amount of research has already gone into gene therapy and the development of vectors for delivering the therapeutic gene into the target cells. The most common vector used currently are viruses that have undergone modifications to render them safe. Yet this does not mean that viral vectors are not without faults…
The Problem: Viral Vectors & Packaging Capacity
Viral gene therapy has been around since the 1980’s, and several viruses have been developed to be of therapeutic use. Yet, they all face a common problem: they are too small. Viral vectors work by packaging the therapeutic gene into their capsid coats in substitution for their own genomes. Yet they are limited in the size of the gene that they can package - only 8-10kB. In order to expand their therapeutic potential, viral vectors need to be able to package larger candidate genes. This would transform the treatment of not only rare genetic diseases with larger genes but genetic disorders in general.
Hover over the capsid!
We are Capacity.
Below is our team, KCL iGEM 2019, who has worked tirelessly throughout the summer to develop a solution to the issue of capacity in viral capsids. This has resulted in our two softwares.
Small RNAs are innovative yet cell-friendly synthetic technology which can be used to down regulate the quantity of a cellular component. Our part collection is made of three sRNAs which are the active component of RNA interference, each inserted into the plasmid with different ribosomal binding site and down-regulating the expression of targeted gene. With the collection, we could investigate the fine tuning mechanisms for gene expression and synthetically engineer bacterial short RNAs to precisely regulate protein translation. This offers effective regulatory system and easier designing method by using Watson-Crick base pairing and bypassing unpredictable structural protein-protein interaction. Our molecular constructs and approach can be used to regulate the ratio of viral capsid proteins to advance novel gene therapy applications.
To address the issue of viral packaging capacity we have developed two software tools: CapsidOptimiser and CapsidBuilder. CapsidOptimser is a software tool that allows us to calculate new icosahedral geometries to design novel theoretical viral capsids with optimised packaging capacities for the delivery of a select gene associated with a rare genetic disease. CapsidBuilder is a software tool that investigates the feasibility of novel viral capsid construction using the constructs from our wetlab. Both of these software tools address how we could potentially build novel therapeutic viral capsids.
Aside from working in the lab, we got really involved with the public. It is crucial to have a strong connection between the public and the scientific realm, yet there is still a significant rift between the two. We aimed to fill this gap with our numerous school visits, talks, and videos that communicate not only our project but what it means to research synthetic biology and genetic engineering.
Not only did we engage with the public but we responded to their thoughts and worries by modifying our project and by developing a series of activities, surveys, and pamphlets to help lessen these concerns. In particular, we placed strong emphasis on biosecurity, as our software tools have the potential to cause serious damage due to the involvement of viruses. We explored this and more during our human practices.
Check out our team video!