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Essentially, we [used human stem cells] to make a mouse continuously produce all the immune cells of a human while all its other cells were of mouse origin. And when these mice are infected with HIV, you start seeing the decline in T cells afterwards, just like you would in the human body. So in the control, mice that were not given the short RNA molecules, we infected them with HIV, and they showed a very rapid decline in T cells about a week after infection. They were at almost negligible levels of T cells two weeks after infection with HIV. But in the mice who received the short RNA molecules, the T cell levels were very similar to healthy mice. The siRNA molecules were able to totally control the infection.

These mice were given the RNA before they were infected with the virus? Like a vaccine?
Yes, it was being used as a preventive drug. But we also wanted to look at what happened if it was administered post-infection. In that case, we created mice with T cells that had already been exposed to HIV. In these, we saw very high viral loads at first. But once they received the RNA molecules, they were able to control the virus. When we administered the RNA weekly, we found absolutely no drop in T cells. Two of the mice did not show any viral load at all.

No viral load? Does that mean you cured these mice of HIV?
I wouldn't say it's a cure. The problem is that these RNA molecules are transient. They stay in the system only for a short period of time, so you'd have to administer them repeatedly to keep the virus at bay.

How long did the effect last?
In the mouse, we could pick up the presence of the RNA molecules for about nine days. By the ninth day we saw a decline. But that's just for mice.

You wouldn't expect a similar nine-day effectiveness in humans?
Right.

Do you worry that, like the most recent HIV vaccine candidate, this technique might work in lab animals but fail in humans?
Definitely. Several things have to be addressed before we take it into higher animal models. For instance, the antibody we're using right now to deliver the RNA molecules is a mouse antibody. It does not cause any adverse effects in mice. But you cannot administer it to humans repeatedly without any kind of immune consequences. The second thing is the amount of RNA we deliver. Right now, we need at least two antibody molecules to carry in one molecule of RNA into the T cells. That means we can't deliver a large amount of RNA. That is not something you can stick with in humans. We'd have to attach the RNA to another type of molecule instead.