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Gene therapy has been long sought after in biology. Its applications are extremely wide ranging, as by manipulating the genome a cell, you can in theory completely manipulate a cell to make it do whatever you want. This is essentially the same goal as synthetic biology, however the key difference is that gene therapy focuses on modifying the genes of cells in animals that have already grown beyond embryonic stage, rather than individual cells on their own. There are many problems with current gene therapy, including it being dangerous, being extremely difficult to perform, its possibility of modifying the DNA of cells in ways that can't be predicted, or the gene therapy not being permanent. Our project is to try and solve some of these problems by using a type of RNA called a 'replicon'.

What is a replicon?

A replicon is RNA that acts to replicate itself on its own using only the ribozymes of the cell. RNA usually degrades very quickly in cells, but a replicon should last permanently, because it should replicate faster than it can be degraded. Several viruses use replicons as their method of manipulating cells. Our idea is to take parts from the genome of hepatitis C (HCV) and modify it so that instead of doing damage to the body, it 'silences' harmful genes. To do this, we want to add an siRNA sequence to a replicon sequence. siRNA (small interfering RNA) is RNA that contains part of a complimentary nucleotide sequence to a particular RNA sequence. The human cell breaks this sequence down, and then continues to break down complimentary RNA sequences to this, including the sequence we want to target.

What are the advantages of this over conventional gene therapy?

Nowhere in this process is the actual DNA of the cell modified, so this removes the danger of DNA of the cell being modified in a way that is unwanted. This also improves upon conventional gene silencing, which involves siRNA only, as the replicon represents a permanent source of siRNA, greatly increasing the efficiency of the gene silencing. Our proposed method of delivery is to use a viral vector, technology which unfortunately doesn't exist yet, but could be developed within the next few decades. This method would allow for gene silencing in multicellular organisms, the holy grail of gene therapy.

Our motivation

'''Diabetes''' The majority of our siRNA testing will revolve around inhibiting DPP-IV, which acts to inhibit insulin. If our system works, it could act as a permanent treatment for type II diabetes. Diabetes kills approximately 3.4 million people per year.

'''Ebola''' Current treatments for Ebola already use gene silencing as a treatment, and our system could improve its effect, by acting as essentially a vaccine for Ebola.

'''Alzheimer's'''

'''liver cancer'''

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