Gene therapy for color blindness

How’s this for weird? This past semester I did a paper on color blindness, citing the different types, where the mutations occur, and the newest research. I was just about to post about one specific breakthrough when I got distracted by a list of the top scientific breakthroughs of 2009. As it turns out, number one has to do with gene therapy.

Two boys with X-linked adrenoleukodystrophy, a disease that ravages the brain, are doing well after French doctors gave them a gene that helps to maintain the delicate myelin coating on their nerve cells. A woman with Pachyonychia Congenita, a painful skin condition, watched one of her sores fade after doctors switched off the offending protein with a newer kind of gene therapy called RNA interference. Twelve patients who were blinded by Leber’s congenital amaurosis showed signs of recovery after getting a genetic treatment in one of their eyes. Italian researchers announced that most of the 10 patients who received gene therapy for severe combined immunodeficiency, or “bubble boy disease,” are doing very well eight years after the procedure that repaired their defenses against infection.

I especially love the implementation of RNAi. I strongly suspect its use will only increase in the coming years, especially in the fight against cancer.

Also this year, researchers at the University of Washington cured two adult monkeys of colorblindness by giving them injections of a gene that produces pigments necessary for color vision. After the treatment, the animals scored higher on a computerized color blindness test.

This one hits especially close to home. I also ‘suffer’ from color blindness, so I find it incredibly uplifting that I may not feel like I’m missing out on the things everyone else is seeing for the rest of my life. It isn’t that I can’t see color – I can – but colors become far less vibrant to me in lesser lighting. This happens to all humans, but it happens to those with color blindness sooner. I also cannot make fine distinctions, like the ones you see (literally) in the Cambridge Colour Test for color blindness. Take this for instance.

Most people will see a “6” there. I can make out some discoloration and the vague shape of a 6, but I wouldn’t be able to guess it without already knowing what to expect. I am likely deuteranomalous. It’s a pretty common type of color deficiency and it doesn’t especially affect daily life – I didn’t know I had it until 3 or 4 years ago during a routine eye exam (which I no longer need thanks to LASIK).

(And blah blah blah your monitor may suck or you may suck at coming up with a balanced coloring, so that test may not show up correctly in the first place.)

RNAi

RNAi is an arrestingly interesting little mechanism for protecting the health of cells. The “i” stands for interference, and with good reason. RNAi is made up of a series of molecules which work to detect and destroy possible viruses and RNA which could be viruses.

It was first detected in 1986 when an attempt was made to make a really, really purple flower. The reason was purely for aesthetics, but it would prove to be far more important.

Knowing the gene which coded for purple pigmentation in petunias, geneticists made the logical conclusion and figured adding a bunch of those genes to the flowers would increase the depth of purple coloring in them. But as it turned out, they were wrong. In fact, they were remarkably wrong. Instead of deep purple flowers, they produced white flowers. Not a hint of purple anywhere.

No one had an answer to why would be. It took 12 years until researchers came up with the answer (and another 8 until they were awarded a Nobel Prize).

When viruses invade a cell, they ‘seek’ to make copies of themselves by utilizing the available DNA source. Post-transcription, this comes out with a funny shape due to the RNA making a mirror image of itself. The RNAi then recognizes this strange shape and destroys it with dicers. But it doesn’t stop there. Any sequence which comes out of the nucleus thereafter is also destroyed. This prevents any of the viruses (hopefully) from being translated and replicating (thus exploding out of the cell and infecting other cells).

Something similar happened when the geneticists tried making the super purple flowers. There wasn’t a mirror-image RNA sequence, but there was a funny sort of shape created by all the extra purple pigmentation genes. The RNAi recognized this as a potential virus and began destroying it. All of it. This meant there were no genes for purple getting translated into proteins.

Example petunia plants in which genes for pigmentation are silenced by RNAi. (http://en.wikipedia.org/wiki/Rnai)

Example petunia plants in which genes for pigmentation are silenced by RNAi. (http://en.wikipedia.org/wiki/Rnai)

So far this is pretty exciting stuff. It’s a post-transcriptional defense mechanism against viruses no one ever knew existed. But it has so much more potential than just as a passing curiosity.

Think about it. If RNAi can essentially turn off genes by destroying them through a sort of sequence-detection, then what stops it from curing diseases? This discovery has the serious potential to cure all the major ailments facing the world today: AIDS, cancer, Alzheimer’s. There has already been success in treating macular degeneration. This is a disease where too many blood vessels are growing in the eye. It damages the retina over time and makes vision majorly cloudy and blurry. There are simply too many genes for blood vessels being produced. But one way to stop this disease is to stop that blood vessel growth. To achieve this, a patient is given an injection which contains a copy of the gene with its mirror image (two mirror strands of DNA). The RNAi detects this misshape and destroys it. It then destroys all other likewise sequences. The same principle could be applied to any number of diseases.

There is an excellent NOVA video on RNAi which can be viewed here. It’s certainly worth watching (and only 15 minutes long).