More gene therapy for more kinds of blindness!

This therapy isnt perfect, but its a cool start!

Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial

'Choroideremia' is a kind of blindness caused by deletion of a gene called REP1. Because REP1 is on the X-chromosome, there is  no 'second chance gene' on the other chromosome in men. They have no functional REP1, so, men with this deletion get choroideremia.

This makes treating choroideremia with gene therapy attractive because we know what is going on. It is not an overly complex network-- its a deleted gene that is causing the trouble. We can make a virus to deliver a functional copy of that gene. Heck, it is even great the gene is actually deleted instead of just mutated-- the 'new' functional gene wont be competing with junk REP1 RNA.

Choroideremia is also attractive in that though it shows itself when people are rather young (night blindness), someone can have the deleted REP1 gene and have normal-ish vision until they are middle aged. That means in contrast with a disease like Lebers congenital amaurosis, where patients are going blind, damage is occurring from the day they are born, with choroideremia, they have a long window where scientists might be able to treat patients BEFORE they lose their vision. And boy to choroideremia patients lose their vision. Its like the whole back of their eye disintegrates :-/

Choroideremia derives its name from the almost complete loss of the retina, choroid, and retinal pigment epithelium that leads to exposure of the underlying white sclera...


So choroideremia provides scientists with a novel opportunity-- A disease caused by one defective gene, gene test/screening is readily available, symptoms show up early, severe damage does not occur until late.

Can scientists deliver a functional copy of REP1 early and prevent REP1-negative men from developing  choroideremia?


From the paper, it was the two patients who had the most damage pre-treatment that got the most benefit. BUT, since the disease takes so long to develop, maybe the remaining patients will see a benefit in 10, 20, 30 years.

Maybe not.

But it is a very cool first step and a novel way to study what gene therapy can do.

They also used a freaking cool GMO virus :-D

  1. AAV2 core.
  2. Chicken β actin promoter. Yes, chicken.
  3. Human REP1 gene.
  4. Woodchuck hepatitis virus post-translational regulatory element. Yes, a woodchuck virus.


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Paul Loebe pointed me toward your blog, and I'm glad he did. I've been reading it for a few weeks now, and I appreciate the clarity you bring to these issues. I have some education in biology and chemistry, but this stuff can get really esoteric.

Thank you for making these things easy to understand.

By Joshua Derke (not verified) on 23 Jan 2014 #permalink

Thanks, Joshua!

Ive been really busy with graduating/moving/new job, but if you click on the "Keywords: Gene Therapy" you can find all the posts Ive written on this :)

Gene therapy via viruses is The Future. LOVE IT!

Potentially naive question here (I'm not overly familiar with gene therapy vectors), but is the actin promoter (e.g. one of the most active promoters in our/chickens bodies) and a post-translational enhancer overkill? Any cell which incorporates this vector will express huge amounts of this protein - and its not secreted, so its not like its high production in a few cells can "fix" the surrounding non-transfected cells.

It would seem to me you'd want a vector that would express this protein at levels more akin to normal biological levels; not at the super-high rates that this vector would appear to create.

Hi Bryan!

Not a naive question at all! I would have to investigate this particular virus/promoter combination, but generally one of the difficulties with this kind of therapy is the DNA gets delivered... and it gets silenced. The trouble has been more along the lines of not enough, rather than too much-- Im guessing thats why they jump through so many hoops to get 'more' rather than 'less' :)

I've been following the work of Sangamo Biosciences and their ZFN (zinc finger nucleotide) method of delivering altered genes or gene replacements. Would their approach be useful in treating choroideremia?

By Jack Funk (not verified) on 27 Jan 2014 #permalink

ZFN, triplex-mediated recombination and other molecular means of gene replacement (as in foreign DNA stably integrated into chromosome by not-virus mechanism), is highly inefficient, and that's when you have direct access to transfect the cells with your materials. The retina is now what I would call readily accessible.

BTW, the N in ZFN is for nuclease, not nucleotide.