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SPEAKER 1: Gene therapy can be delivered intrathecally with lumbar puncture or what are the limitations? Why do you believe that gene therapy has to be delivered intraparenchymally with a neurosurgical approach?

SPEAKER 2: Another great question. And that can be answered two ways. One, with our approaches that we've developed for Parkinson's disease, it's very important that we remain very focused in terms of specific region of the brain that we'd like to transduce. So that is not possible with vectors which are being delivered through the, let's say, intrathecal space, because the off-target transduction is extremely high. So the targeted delivery that we can obtain by direct infusion of the viral vectors into the brain is what really provides us with a few things. One, it's a very precise targeting within the area of the brain that we would like to treat, but also dramatically reduces any possible immune responses that would be otherwise present with the systemic administration.

And then, as I said, it also will limit the off-target transduction in the areas of the brain that we may not want to express those particular genes in terms of both AADC and GDNF, these things are very, very important to us.

And lastly, I'd like to mention that we have learned how to utilize the [INAUDIBLE] tropism of these particular viral vectors we'd be using-- there are many serotypes of the adeno-associated viral vectors-- but also learn how to utilize the neuronal pathways within the brain to really disseminate the gene expression. So by understanding the pathology, but also neuroanatomy, we can target small part of the brain, just as we're doing it in Parkinson's, and utilize the neuronal projections to deliver the payload into the terminal areas, which would be much more diffuse, very often, than our target.