Author Topic: Gene therapy  (Read 1897 times)

Offline Elite

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Gene therapy
« on: February 17, 2006, 12:28:34 PM »
I have some questions regarding gene therapy (introduction of DNA into cells using virus vectors) for Shvarz:

1) Is it possible to replace ALL of the DNA in a cell with new DNA via the vector, ie. replace the cell's entire genome with a new one? (viruses do this don't they?)

2) Is it possible to radically alter the entire genome of a complete living thing? What would happen in an extreme case, say of replacing a mouse's DNA with that of a frog?

3) Would cells with new DNA and a new function or shape change to fit their new function, or would they stay specialized as they were before the DNA introduction?

4) How much DNA can one vector hold?

Offline shvarz

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Gene therapy
« Reply #1 on: February 17, 2006, 06:02:19 PM »
Quote
1) Is it possible to replace ALL of the DNA in a cell with new DNA via the vector, ie. replace the cell's entire genome with a new one? (viruses do this don't they?)

4) How much DNA can one vector hold?

The most common vectors for gene therapy are retroviruses. They can hold up to 10,000 bases (10^4).  Our genome is 10^9.  So obviously replacement of a complete genome with a vector is out of the question.

Quote
2) Is it possible to radically alter the entire genome of a complete living thing? What would happen in an extreme case, say of replacing a mouse's DNA with that of a frog?

What can be done, however, is to take out entire nucleus (DNA, RNA, protein and everything else) and inject a different nucleus.  But that is done on the level of individual cells and many of these cells don't survive the procedure.  I'm not sure if anyone tried to use different species and what the result was if they did (I'll ask my wife tonight, she might know).

Quote
3) Would cells with new DNA and a new function or shape change to fit their new function, or would they stay specialized as they were before the DNA introduction? 

Again, I don't know the answer to your exact question.  What I know is that in cloning experiments with sheep and dog and others, people took nucleus from a specialized cell from one animal and put it in place of nucleus of an unfertilized egg and that resulted in non-differentiated cell that could give rise to the whole organism.
"Never underestimate the power of stupid things in big numbers" - Serious Sam

Offline Elite

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Gene therapy
« Reply #2 on: February 17, 2006, 06:23:22 PM »
Thanks for that  :D

I was thinking that a mimivirus would be able to carry such a vector, but they are again too small (800,000).

Is there any other way to inject a human-sized genome into a cell in vivo?

Ah, cloning, I'd forgotten about that. Me and a friend were debating what would happen if a living organism's DNA was miraculously replaced with the DNA of a different organism, either:
1) The organism would transform into the organism from which the DNA came
or
2) The organism would fall apart

Offline Numsgil

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Gene therapy
« Reply #3 on: February 17, 2006, 07:54:02 PM »
This is what I imagine would happen if you magically found a way to alter all the DNA in an organism at once:

1.  Rejection:  Eventually the organism's immune system would produce new immune cells.  These cells would come to recognize the original body tissue marker protiens as foreign, and you'd have the body rejecting itself.

2.  If rejection was suppressed (say, through some serious drugs) you'd probably end up with all sorts of cancers.  DNA has many epigenetic control proteins that control expression by physically existing on the DNA strand, blocking transcription.

3.  If that wasn't enough, and you managed to get all the DNA function correctly, then you'd end up with cells that frequently repopulate themselves beginning to mimic that of the donor DNA.  Specifically, skin cells, blood cells, etc.  Cells that rarely reproduce, such as nerve cells, would have less dramatic changes.  Assuming the two organisms' DNA is similar enough, there might not be any difference at all.

So, in your frog/mouse example, I'd say it's probable the mouse would eventually develop frog like skin and blood, but it's skeletal form would remain that of a mouse.

Just my guess anyway.  It's all hypothetical anyway.

Offline Elite

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Gene therapy
« Reply #4 on: February 18, 2006, 06:55:27 AM »
Very interesting. So you'd probably have to use multiple coctails of drugs that supress rejection and stimulate temporary cell division. And find a way to make sure the epigenetic proteins stay intact.

Doesn't the phosphate backbone have something to do with switching genes on and off?

How is DNA actually 'coded' - I know it's not a real language and it's a complete mess - but are there any 'instructions' that DNA uses or is it controlled by the interactions of the proteins made from each set of each three base pairs.

EDIT: Found a wikipedia article
 - I assume proteins are assembled from sequences of amino acids after they have been copied to RNA, and then these proteins carry out tasks for the cell to function. Is this right?
« Last Edit: February 18, 2006, 08:42:58 AM by Elite »

Offline Welwordion

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Gene therapy
« Reply #5 on: April 28, 2006, 05:42:48 PM »
A problem with interspecies transfer is, that ribosomal Dna is independent from nucleus Dna such the nucleues might not find the right "tools", the organells might not be compatible with the nucleus commands.
As for a method, I read an article about cell fusing, which allows two foreign cells to form any hybrid and seems  sometimes naturally occur when foreign cells are introduced, such if the old nucleus would be somehow destroyed by the new one this would solve the problem.
A further problem is biochemical compatibility certain enzymes, hormones might not work with existing receptors as well as certain stuff like insulin might not be produced correctly.
Also as the metabolism is optimized to certain temperatures, energy consumption rates and type of foods there might be a large drop in effectivity of the whole system.

Offline Numsgil

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Gene therapy
« Reply #6 on: April 28, 2006, 06:21:55 PM »
Note that the problems of not finding the right tools are greatly reduced the closer the animals are related.  Between vertebrates there probably isn't too much issue.  Between animals and plants there are some serious issues.  Between bacteria and eukaryotes, there's some serious serious issues.