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As the question states, what are the limits of retroviral genetic delivery systems?

Are they limited to adding additional gene sequences to a cell, or can they actually overwrite specified segments of DNA?

Or, more aptly described, can they remove one segment of DNA, and insert a new segment (whether the same or different length) in the spot where the old segment used to be?

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To me "overwriting" seems to imply limited memory (e.g. based on using computer memory as a metaphor for DNA), while changes in DNA are due to deletion, insertion and single base mutations (substitutions). Chromosomal translocations are another case (as deletion->insertion). –  fileunderwater Aug 28 '13 at 20:57
    
Well, I am a programmer, so that is the first metaphor that comes to mind for me. :) . I'll reword and clarify a bit. –  eidylon Aug 28 '13 at 20:58
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2 Answers

up vote 3 down vote accepted

Retroviruses, such as HIV, have a genome that is composed of RNA. Once inside the host cell, that RNA is reverse-transcribed into DNA; it is that DNA which is inserted into the host genome. All retroviral genomes are integrated through insertion; there is never any replacement.

Some retroviruses do, however, disrupt normal gene function. Mouse mammary tumor virus (MMTV) or Human T-lymphotropic viurs (HTLV) will often insert inside or near host genes termed "oncogenes," that, when disrupted, can lead to cancer formation.1,2 Viruses could cause up to 15% of cancers in humans.3 So, no actual genetic replacement, but there can definitely be genetic disruption and a deleterious functional change.

This ability, to insert new genes, has recently been touted as a new way to cure many diseases. Here's the most recent case, where the researchers used a retroviral backbone to insert a functional gene into some children; i.e., genetic engineering (Side note: Every time you see an article saying how scientists used HIV to cure a disease or something, this is what they mean. It's akin to calling dental X-rays "giant death lasers that fight cavities."). With luck we will get better and better at it, but right now it's only successful in limited cases for very specific diseases; massive genetic engineering of humans is still far off (unless you count bone marrow transplants).

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Nice answer, but a few references (especially for the removal function) would be great. –  fileunderwater Aug 28 '13 at 21:06
    
A friend is telling me about genetics research she has worked on regarding treating Huntington's disease, but that a true cure would be hard because it's genetic. So not being a geneticist, the first thing came to mind was well, use a retrovirus to deliver a cure. Would an RV be able to add code then which 'disrupts' the faulty genes, and add new code which does what the bad ones should've been doing? –  eidylon Aug 28 '13 at 21:07
    
@fileunderwater I added a few references, in particular a solid review. It's not a particularly new concept so there's plenty out there. –  Amory Aug 28 '13 at 21:29
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@eidylon I tried to answer your question a bit, pointing to some research people are currently doing. GE on that scale is still a long ways away but it's amazing the strides we're making right now. –  Amory Aug 28 '13 at 21:29
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Just to give a simpler example of what Amory has explained. Viruses can overwrite existing information, just not the way you would think if coming from the world of computers.

As already mentioned, viruses have the ability to insert their genetic information into the host's genome. They do this by essentially cutting the host DNA open and inserting themselves between the cuts. This insertion can disrupt a gene, thereby, in a sense, overwriting it.

To take a simple metaphor, consider the following sentence (a "gene"):

Hello, my name is Bob.

If I were to insert a new sequence of characters into that sentence, it's meaning would be lost:

Hellalkehfgawpif galsdhfblasud hyflaishbflaegfvlhD BFHDFLHFEiDBFKHDBfo, my name is Bob

While the original sentence is still there so it has not been overwritten in the strictest sense of the term, the information it contains has now been lost to the cell so the result is the same.

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