HIV virions budding from a cultured lymphocyte

What is an HIV virus that doesn't cause HIV?

It might be the key to medical cures based on genetics.

Since we've decoded the human genome, a tantalizing prospect has loomed before researchers and the medical community: gene therapy. If we can understand what genes cause an illness or defect, and if we can repair or replace them with a more desirable alternative, then we can correct problems at a cellular level. Gene therapy is non-invasive. The body fundamentally reforms itself, and new cells that grow after treatment follow the new, improved blueprint in the altered DNA.

We grow new cells all the time, not only when we're healing from an injury. For instance, our constantly regenerating skin gives us entirely new palms every 24 to 48 hours. In fact, our entire bodies rebuild themselves about every 7 years. Why not take advantage of this constant growth and replacement cycle to literally build "a new you", free of whatever was ailing you?

Scientists have been thinking about this for quite a while.

Two Gene Therapy Obstacles

This approach to medicine and genetics faces two major challenges. One is our as-yet limited knowledge about which particular genes are responsible for a given set of traits, symptoms and syndromes we have identified. Simply mapping the human genome is not enough: this gives us a map, yes, but as they say, the map is not the terrain. Does this bit of genetic code here affect your reaction to stress, or does it control your affinity for alcohol? Deciphering these linkages is an ongoing process. We're making progress, but so far have only scratched the surface.

The other major hurdle is how to alter genes once we know what section of code is relevant to a problem. DNA can be segmented - removing a related chunk of code, like pulling a clause out of a sentence - and a new segment spliced in its place. This process involves specialized enzymes and careful gene mapping to identify the segments being tweaked, and lends itself best to laboratory manipulation.

Yet DNA can be changed in another way, as well: it can be rewritten in place in a human body, physically altered in situ. If we can rewrite the genetic code in place, nothing needs to be removed and reinserted. Ideally, once initiated, DNA alteration would continue automatically within the subject's own body. But this neat solution is significantly more challenging. How do we work on the submicronic level to rewrite a body's genetic code?

HIV to the Rescue

The answer, surprisingly, may be HIV. Viruses survive by attaching themselves to host cells and rewriting segments of DNA to replicate themselves. HIV is so pernicious in part because it infiltrates the body so thoroughly and does such an aggressive job of reprogramming the host's genetic code and replicating itself. Unlike most viruses it can even penetrate stem cells, to reformulate the code of the basic building blocks of the human body.

Now, in a ground-breaking therapy, a team if French scientists have stripped the HIV virus of its deadly components and used it as the vehicle to carry tailored genetic code into two host bodies.

A team led by Dr. Patrick Aubourg of the University of Paris-Descartes has been working on a treatment for ALD (adrenoleukodystrohpy), made famous in the movie "Lorenzo's Oil." In its worst form, the disease destroys the coating of nerve fibers in boys' brains, causing a breakdown of the neurological system. ALD typically strikes between the ages of 4 and 10, leading to loss of sight, hearing, muscle control, dementia, and then to death within a few years.

An AP report describes their groundbreaking work:

Bone marrow transplants can halt ALD by letting new myelin-forming stem cells take root. But it's difficult to find a matching marrow donor, and the transplant itself is very risky.

So what if stem cells from the boys' own bone marrow could be genetically corrected, eliminating the ALD mutation? To do that, Aubourg's team had to overcome a technical hurdle: Gene therapy works when scientists harness deliver a healthy new gene by attaching to a virus that can harmlessly infect cells. But none of today's so-called gene therapy "vectors" could penetrate enough of the stem cells needed for an ALD treatment to work.

Unlike most viruses, HIV can penetrate stem cells, and it sticks permanently. So Aubourg's team removed the genetic parts of HIV that make it dangerous, leaving basically a scaffolding to carry the new therapeutic gene.

Then they culled stem cells from two 7-year-old boys in the early stages of ALD, and mixed in the healthy gene. The boys underwent bone marrow-destroying chemotherapy and then had their genetically corrected stem cells reinserted.

Two years later, the boys have shown no sign of worsening brain damage and are functioning well with 15 percent of their blood cells producing the healthy protein, said Aubourg, who plans to test the experimental procedure in more patients.

Let's think about that for a minute.

Scientists have now established a way to use a virus successfully in gene therapy. They strip HIV down to a delivery platform devoid of its ordinary effects and load it up with the DNA they want to replicate. The virus infiltrates cells where it delivers its payload of correctly-programmed genetic code into the host's system. It is especially good at glomming on to stem cells.

In typical aggressive HIV manner, this virus digs in, rewrites DNA, reproduces, spreads, and repeats its life cycle in every cell it can get a toehold in. Meanwhile, the stem cells grow and differentiate as they are supposed to, following not only the template of whatever cells they are administered with (in a cell therapy regimen), but also the encoding injected into them by the modified HIV virus.

With cell growth over time, this is a huge hit of Correct DNA, perfectly positioned to reproduce within the host. And voilà: the hurdle of 'how to effectively deliver rewritten DNA' is leapt.

Now That We've Got That Licked...

As we continue to figure out what genes link to what diseases or defects, we will be able to create gene therapies for more and more illnesses. And, potentially, not only illnesses but congenital defects. And then, maybe, unwanted tendencies - male pattern baldness, a slow metabolism that packs on pounds - and of course the obvious easy tweaks in the cosmetic realm, like eye and hair color, or the shape of a nose or jaw line.

At what point might we tackle encoding desireable traits, not just erasing unwanted ones? How about ensuring fast-twitch muscle reflexes for your future Big League Slugger, or a high IQ for the designer baby destined for Harvard?

And here life begins to imitate the art of science fiction.

In Part 2, I'll take a look at what science fiction fears and foresees in the realm of gene therapy and its kissing cousin, tailored genes.