MadSci Network: Molecular Biology
Query:

Re: Restiction enzymes in humans

Date: Thu May 22 18:41:07 2003
Posted By: Jim Caryl, Grad student, PhD Biochemistry & Molecular Biology
Area of science: Molecular Biology
ID: 1053319322.Mb
Message:



It is certainly a nice idea in theory, as was the idea of introducing functioning genes into human DNA by chromosomal insertion of viral DNA. The trouble is, that approach at gene therapy has run into significant problems. The trouble with restriction enzymes is that they are highly specific and require specific chemical conditions in which they are active. The first problem would be introducing them. For them to have a realistic action they would have to be intracellular as viral DNA is protected by a capsid and will be resistant to enzymatic attack. The point of action would have to be when (and if) the virus release their DNA as they try to become lysogenic (inserted into the host DNA).

So to have the restriction enzymes intracellularly, they would need to be introduced as genes and expressed by the host cells. This in itself is a major feat as the introduction of natural human genes stably has proved difficult enough.

Assuming you a) managed to get the restriction enzymes into position, and b) managed to get them expressed into a chemical environment where they are active and not degraded by host cellular proteases, then the next task to to have them cut viral DNA specifically. Unfortunately this is where the theory trips up because specific as restriction enzymes are, they are not as specific as that. Perhaps the largest specificity sequence of any restriction enzyme is about 20 bp, usually they vary between 3 to 7 bp. So you have to find a restriction enzyme that is specific for a DNA sequence that doesn't occur in humans (you can't after all engineer one as that is just not accepted in society) , and this sequence has to be suitably deleterious to virus replication. Given the size of the human genome, it is likely that the viral DNA (if exposed) would be cut at the cost of the host cellular DNA (though this itself has a measure of protection) and either way result in cell death and liberation of the virus - which would just exacerbate the cellular / tissue injury caused by the virus.

I've just presented the main points against. There are others, but you get the picture. So like many ideas, it sounds an inventive one in theory, but unfortunately it wouldn't be practicable.

Jim

MAD Scientist


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