The past week’s Chalk Talks carried lots of interesting information about the amazing research being conducted here at Duke. One of the presentations that caught my eye was by Nico Rey, who talked about his experiences at the Asokan Lab where they are designing a novel gene therapy for Muscular Dystrophy using viral vectors. The basis of Nico’s research is the Central Dogma, DNA makes RNA makes proteins. In many diseases, there is some error or mutation which occurs in one of these steps which causes the product to become unusable. For Muscular Dystrophy, this occurs in the first step, aka, there is a mutation within the DNA that causes the entire process to result in a failed protein.
Nico’s viral vectors will insert RNA into the cell which will complementary bind to regions of introns preceding a mutated exon which causes an alternative path for polymerase enzymes to take when producing mRNA. These inserts will contain the complement to the correct mRNA exon sequence that we wish to translate into protein. However, Nico noted that the current method of inserting the RNA and leaving it up to chance was relatively inefficient and up to chance. Therefore, his lab is focusing on leveraging novel molecular machinery to increase the odds of forcing enzymes to choose the insert rather than the original mutated DNA.
I remember after hearing Nico’s Chalk Talk that this type of procedure sounded rather familiar, and it seems to resemble a bypass surgery, where a vascular graft is taken to bypass a clotted region to provide blood to tissue. In a similar sense, here Nico’s lab is bypassing the mutated and ‘diseased’ DNA to allow for the cell to exhibit the healthy phenotype. I think that this technology is a really good way to tackle disease as it leverages viral vectors which are known to work, inserts a small amount of specific RNA which we know will only bind to the regions we want, and has the potential to greatly alleviate symptoms of debilitating diseases.