A Drug To Re-Awaken Ancient Human Genes And Fight HIV

"Junk DNA" are inactive parts of your genome, switched off long ago in evolutionary history. Now scientists say there's a junk gene that fights HIV. And they've discovered how to turn it back on.

What these scientists have done could give us the first foolproof HIV vaccine. They have re-awakened the human genome's latent potential to make us all into HIV-resistant creatures. This evening in PLoS Biology, they've published their ground-breaking research.

A group of scientists led by Nitya Venkataraman and Alexander Colewhether wanted to try a new approach to fighting HIV - one that worked with the body's own immune system. They knew Old World monkeys had a built-in immunity to HIV: a protein called retrocyclin, which can prevent HIV from entering cell walls and starting an infection. So they began poring over the human genome, looking to see if humans had a latent gene that could manufacture retrocyclin too. It turned out that we did, but a "nonsense mutation" in the gene had turned it off at some point in our evolutionary history.

Nonsense mutations are caused when random DNA code shows up in the middle of a gene, preventing it from beginning the process of manufacturing proteins in the cell. Venkataraman and her team decided to investigate this gene further, doing a series of tests to see if the retrocyclin it produced would keep HIV out of human cells. It did.

At last, they knew that if they could just figure out a way to reawaken the "junk" gene that creates retrocyclin in humans, they might be able to stop HIV infections. The researchers just needed to figure out a way to remove that nonsense mutation and get the target gene to start manufacturing retrocyclin again.

Here's where things really get interesting. The team found a way to use a compound called aminoglycosides, which itself can cause errors when RNA transcribes information from DNA to make proteins. But this time, the aminoglycoside error would work in their favor: It would cause that RNA to ignore the nonsense mutation in the junk gene, and therefore start making retrocyclin again. In preliminary tests, their scheme worked. The human cells made retrocyclin, fended off HIV, and effectively became AIDS-resistant. And it was done entirely using the latent potential in the so-called junk DNA of the human genome.

After more research is done, the researchers believe this might become a viable way to make humans immune to HIV infection.

What intrigues me, beyond the amazing idea of an AIDS vaccine, is that aminoglycosides have the potential to unlock the uses for other pieces of junk DNA. Those of you who read Greg Bear's novel Darwin's Radio know that this scenario is familiar scifi territory: In that book, humans start rapidly evolving after their junk DNA re-awakens in response to stress. Could we induce instant mutations, or gain other new immunities by using aminoglycosides on our junk DNA? What would it mean to have the whole crazy, giant human genome at our command?

via PLoS Biology