Science Sunday: 'Tricks' Of The Trade

AllTheGenesThatFit
VectorVille


So.

We've sequenced the human genome and we've identified a bunch of small chunks (ie. genes) that are messed-up and/or mutated in a bunch of different diseases.

So (again).

What's the problem?

I mean, why haven't we fixed all these diseases by putting in good genes that aren't messed-up in the cells that need them.

Well, it turns out that the real problem is that we've been unable to figure out how to get those fixed genes into the cells that need them in an efficient and non-toxic manner.

We've tried all kinds of ways to do it, including using otherwise crippled viruses as a 'vector' to deliver them.

But there have always been all kinds of problems and concerns, some of them really, really bad that have put the kibosh on full steam-ahead 'Gene Therapy' for quite some time.

Until, maybe...... now.

Here's the somewhat breathy NPR report on the very recent breakthrough:

"Researchers in France have successfully treated two young boys with a rare but fatal genetic disease. This marks a high point for the field of gene therapy after several well-publicized setbacks.

Patrick Aubourg leads the French research team. Since 1993, he's been working on a disease called X-linked adrenoleukoDYSTROPHY — or ALD. ALD is a devastating neurological disease, incapacitating and ultimately killing people who have it. Many people became familiar with ALD from the 1992 movie Lorenzo's Oil, which featured a young boy affected with this disease.

Since ALD is caused by a single gene, it's an ideal candidate for gene therapy. Put the repaired gene back into patient's cells, and that should fix the problem.

Simple in theory, but in practice, it's been extremely difficult. The biggest hurdle has been finding an efficient way to get the repaired gene into the cells of patients. One of the tricks involves attaching the gene to a virus. The virus acts as a vector, inserting the repaired gene into cells......"

Now, if any climate change deniers and/or Email 'hack and release' experts are reading this, please note the use of the term 'trick' above.

And when you do, please do not make the mistake in inferring that something nefarious is going on, because when cell and molecular biologists figure out an elegant way to do something we often do call those things tricks.

And in fact, in this case, the fine french folks under consideration used three very neat tricks to pull this off.

Here is the less breathy description of what they did, straight from their abstract in the top-of-the-ladder journal 'Science':

....Autologous CD34+ cells were removed from the patients, genetically corrected ex vivo with a lentiviral vector encoding wild-type ABCD1, and then re-infused into the patients after they had received myeloablative treatment.....


So (again, squared).

What does this mean in regular language?

Well, they first isolated Stem cells that are marked by a 'CD34' tag from the bone marrow of the patients themselves (that's the 'autologous' part). Second, they stuck the normal gene into the isolated stem cells while they were in a test tube using a fancyvirus that will get into non-dividing isolated cells (that's the 'lentiviral vector' part). Then, third, they stuck the modified stem cells back into the patients' bodies so that they could get busy and develop normally and do their normal rather than messed-up thing.

And what happened?

Well, so far the following, taken, again, directly from the Science paper's abstract:

"....Beginning 14 to 16 months after infusion of the genetically corrected cells, progressive cerebral demyelination in the two patients stopped...."


Neat tricks, eh?

Oh.

And just so you know, 'cerebral demyelination' is the process that wrecks nerves in the brain that causes the debilitating 'dystrophy' part of the disease.

OK?


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