Gene therapy for mouse vision

Posted on April 9, 2010 by Michael

Gene therapy is generally a good thing. Just last year it was used to cure color blindness in spider monkeys. In that instance, an adeno-virus was used to deliver the correct gene into the primates; that’s often how it is done. However, there are drawbacks to this. For instance, insertional mutagenesis may occur. This is where an inserted sequence causes a change in the expression of a nearby gene. In many cases, this will cause cancer. It doesn’t always happen and not all viruses will be the right kind to integrate themselves into the host’s genome, but the possibility is a very real one. Fortunately for the spider monkeys, no side effects have been noted.

Another way to go about fixing faulty genes is to do what Cai et al. did and deliver the correct DNA via nanoparticles. They injected mice which had retinitis pigmentosa, a disease of the eye, with saline, naked plasmid DNA (i.e., not compacted in a nanoparticle), and with nanoparticle compacted DNA (plus a control group that received nothing). The correct gene, the Rds gene, did nothing when it was given alone (and, of course, the saline did just the same). However, the nanoparticle DNA did prove to have an effect. In fact, not only did it retard further degeneration of vision, but it even caused healing in the form of functional and structural improvements.

There are still safety issues that need to be fleshed out with more research, but this method of correcting faulty genes is both promising and pretty exciting. What’s more, it even has opened the avenue for some good zingers.

“Making the blind see was once called a miracle,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “As we have expanded our understanding of evolution, genetics, and nanotechnology, chances are that “miraculous” cures will become as commonplace as those claimed by faith-healers past and present.”

1. X. Cai, S. M. Conley, Z. Nash, S. J. Fliesler, M. J. Cooper, M. I. Naash. Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa. The FASEB Journal, 2009; DOI: 10.1096/fj.09-139147

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Gene therapy for color blindness

Posted on January 3, 2010 by Michael

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.)

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