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Gene therapy via intracellular parasite

Subcontract that job.
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Gene therapy for inherited diseases is slowly gaining traction. See wikipedia article, linked. In short the theory is that if one has a disease due to misbehavior (usually low activity) of some gene product, it is possible to engineer into that persons cell normal DNA such that gene product activity is normalized and the disease reversed. Hurler's syndrome is a good example: see link.

Problems with gene therapy 1: It is individualized and must be done new for each person. There is no "off the shelf" version. 2: It is risky: gene can insert wrongly and cause cancer, and transplant is dangerous. 3: There is no route to continued profit as is the case for drug therapies.

Consider now intracellular parasites. They are all set up to get into our cells, evade immunity and coexist with us. Malaria is the example I will use but other organisms (rickettsia?) might be even better. Back in olden days benign strains of malaria were used therapeutically; see link. Humans are pretty well evolved to coexist with malaria.

One could genetically engineer a malaria parasite to express a needed gene product. Benefits:

1: Risk is that of malarial infection: much less than risk of genetic engineering a live human or an allogenic bone marrow or liver transplant. One could engineer in exquisite sensitivity to quinine or some other antiparasitic in case things got out of hand and you needed to turn the infection off.

2: Off the shelf one size fits all treatment: a parasite expressing the Hurler's enzyme could be used to treat anyone lacking that enzyme.

3: If the infection burnt out and went away, reinfection!

bungston, Jun 28 2012

Gene therapy http://en.wikipedia.org/wiki/Gene_therapy
[bungston, Jun 28 2012]

Hurlers syndrome http://en.wikipedia...iki/Hurler_syndrome
example of a candidate disease for treatment with gene therapy. The Triple Lindy of such treatments would, of course, be sickle cell. [bungston, Jun 28 2012]

Therapeutic use of malaria http://jama.jamanet...px?articleid=244046
JAMA 1926. Google scholar is awesome! [bungston, Jun 28 2012]

Review of Ted Steel's book http://www.2think.org/lamarck.shtml
What Unabubba is talking about [Loris, Jun 29 2012]

Mind control by toxoplasmosis http://www.theatlan...ing-you-crazy/8873/
The rat stuff is more plausible than the human. But once you buy the rat piece, why not humans too? [bungston, Jul 05 2012]

[link]






       I like the idea, and think it could work well for genetic diseases which are essentially catabolic defects.   

       However, I'm not sure using malaria is such a good idea. Too much morbidity in chronic infection.   

       But - since we're basically talking about digestion, the engineered organism does not necessarily need to actually be within the body. It could instead be in the digestive tract, where there is already a thriving bacterial community. This would then be a symbiotic relationship.   

       Phenylketonuria is a severe disease when untreated, arising from an inability to convert the amino acid phenylalanine into tryrosine (another amino acid). The treatment basically consists of restricting the diet to be low in phenylalanine and supplementing tyrosine. It seems feasible to me to genetically engineer a microorganism like E. coli to perform this task, regulated to leave sufficient phenylalanine for host survival.
Loris, Jun 28 2012
  

       That PKU idea is great. Better than mine. Could work for lots of other metabolic diseases treated with diet.   

       but thinking.... the PKU kids absorb P in the stomach, before the meal has encountered the bacterial populace of the colon. Probably true for other metabolic diseases too.
bungston, Jun 28 2012
  

       Nice idea, at least for those diseases that could be corrected by treating the blood cells (or other cells which intracellular parasites invade).   

       Lots of other apicomplexan parasites (ie, related to Plasmodium) exist, although I think only Plasmodium is tolerated in chronic infections.
MaxwellBuchanan, Jun 28 2012
  

       A intelligence-boosting gene hack using the HIV virus has turned up in fiction..it all going a bit pear shaped and all the animals getting smart.
not_morrison_rm, Jun 28 2012
  

       Intelligent pears? Hmm. Food for thought.
MaxwellBuchanan, Jun 28 2012
  

       How d'ya like THEM apples ?   

       // those diseases that could be corrected by treating the blood cells //   

       There is evidence to support the theory that sickle-cell anemia is an evolutionary adaption that confers a modicum of resistance to malaria, and is therefore selected for in vulnerable populations.   

       So the suggestion that the process could work in reverse is not unfeasible (chicken/egg).
8th of 7, Jun 28 2012
  

       This sort of thing is well under way, in the research of Ted Steele (University of New South Wales). He's been fighting for 20 years or so to get other scientists to recognise his work in the effect of past infection on heritable DNA morphology (as I understand it).
UnaBubba, Jun 28 2012
  

       //work in the effect of past infection on heritable DNA morphology// Link?
MaxwellBuchanan, Jun 29 2012
  

       After poking around a bit I found a link to what Unabubba is talking about.   

       On the basis of that book review, I don't think it's anything particularly exciting.
Loris, Jun 29 2012
  

       We don't want anything heritable. That takes away the repeat business.
bungston, Jun 30 2012
  

       Coincidentally, I was just talking with a colleague who works on Toxoplasma. Toxo gets across the blood-brain barrier, and in some cases maintains a chronic low-level infection. It might, therefore be a useful vector.
MaxwellBuchanan, Jul 05 2012
  

       Toxo would probably be better than malaria. There was a very interesting article on how toxo modifies the behaviors of its host animals - I will link.
bungston, Jul 05 2012
  

       Yes, toxo is interesting in that way. I'm not sure about the behaviour modification in humans - my guess is that Toxo is a recent parasite in humans and hasn't developed that level of interaction.
MaxwellBuchanan, Jul 05 2012
  

       I've read that toxoplasmosis turns you into a Frenchman.
Cuit_au_Four, Jul 06 2012
  
      
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