Angels do dance on the head of a pin, after all

Now when I think of vectors, I generally think of mosquitoes, tsetse flies, and rats. Critters who, while going about their normal businesses with no particular malice towards us, spread assorted plagues through the human population.

Controlling or preventing epidemics often involves controlling the vector.

In fact, until today, I didn’t know there was any other sort of vector. But there is. As it turns out, vector is one of those over-used words that carries very different meanings in various fields of human endeavor.

In mathematics, a vector is a number with size and direction. In design work, it is a type of graphic that changes size without loss of resolution. A vector can also be a course or direction of an aircraft. Or, in genetics, a vector is an agent that transfers genetic material from one cell to another.

Genetic scientists working in the dangerous but promising field of gene therapy are starting to use viruses as vectors the way you and I use FedEx. Virus vectors are used to intentionally deliver gene packages to the inside of human cells.

So here’s my third-grade understanding of gene therapy (I often push the envelope in my recreational reading). A significant number of diseases are caused by broken, missing, or damaged genes. Fixing the gene reverses the disease. Fixing broken genes cell-by-cell is no easy matter, but if you can place repaired genetic code into a cell, the cell will reproduce. Over time the fixed cells start doing whatever job it was the broken cells weren’t doing right and Presto Changeo! The disease is defeated by the body itself. Simple. Elegant. At least on paper. It turns out the devil is in the details.

So why use a virus as the delivery boy?

It is in the very nature of how viruses choose to invade the cells that makes them possible vectors for gene therapy. Viruses are the ultimate Trojan Horses. They have all kinds of tricks up their tiny little sleeves to get past the body’s immune system sentinels and arrive safely inside your body’s cells.

So virus vectors were chosen as the obvious way to deliver the repaired genes into the cells, as viruses like to get into cells anyway. The trick is to engineer the viruses to do what you want it to do, and not necessarily what they evolved to do. If you make the virus too weak, the immune system discovers the invader and wipes out the virus, along with its precious genetic FedEx package of repaired genes. If you make it too strong…

Early gene therapy clinical trials have had some stunning successes in curing an assortment of rare diseases. Successes have included the “Bubble Boy” disease, one sort of blindness, and a rare blood cancer. But the cutting edge trials have also killed some of the participants.

The key to success seems to be a more holistic approach that includes a greater understanding of the role of the immune system in this complex cosmic dance. You can’t just repair the damaged genes, stick them in a virus, and inject them into the human body. You need to really, really, really understand how the immune system is going to react to the vector.

As more research on viruses continued it was discovered by Dr. James Wilson (University of Pennsylvania School of Medicine) that there are at least 120 sub-types of a particular virus called AAV.

AAV viruses seem to have affinity for various organ systems, they prefer certain types of tissue and don’t really care all that much for other regions of the body. Using a AAV virus matched to the organ system for a given disease should prevent run-away infections, the prime suspect in clinical trial deaths, allowing the doctors of the future to choose the right viral delivery service for what ails you.

How amazing is that? Nature may have given us a complete tool kit to repair our damaged bodies. What are the odds?

Viruses, long regarded as the enemy, could prove instead to be angels.