health and medicine question #3062



Owen Richardson, a 17 year old male from Cobble Hill (Vancouver Island, B.C.) asks on November 23, 2005,

Q:

I understand that cancer is caused by mutations in some of the genes that regulate cell growth and division. I also understand that patterns of which genes are likely to mutate, and how they will mutate, are reasonably well understood. Why then can we not use genetic engineering to make artificial viruses with RNA to fix the mutated genes and inject these viruses into tumors? Is there not enough space in a virus shell? If that is the case, then couldn’t we at least make viruses that could break the mutated genes completely?

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the answer

Wendy Hutchins answered on November 7, 2010, A:

Yes, some cancers are in the genes for cell growth and division.  There are three categories of genes that can be mutated: Growth promoters or proto-oncogenes meaning they can promote tumors if mutated, growth regulators usually called tumor supressors, and DNA repair genes.  We need the last category to check that DNA replication is complete and without mistakes. 

In the case of proto-oncogenes, yes, there are people looking at inhibiting the RNA of an oncogene.  This is called RNA interference and it works by making the RNA of a gene degrade faster than it would normally.  Yes, they are using viruses to deliver it to cells in culture.  In the case of tumor supressors and DNA repair genes, you want to replace a missing gene in a tumor to re-introduce that missing controller gene.   Thus, one issue with gene therapy, which is what you are suggesting, is to find the right genes to target. 
 
Another issue with tumors is that they have multiple mutations, not just one.  One mutation may be dormant until another mutation arises (chemical, UV, genetics, infection, whatever cause).  This is called the multiple hit theory of cancer development.  As a tumor moves from benign (contained) to malignant (invasive) and then metastatic (spreading to other tissue), it develops a lot more mutations. 
 
The issue with viruses as therapies has problems too.  Some viruses can take extra DNA or RNA very well and we are using them like that right now.  The issue is to a) prevent an immune response from clearing the virus that is being used as a therapy, b) how to get a virus into certain tissues if the virus is not able to infect those tissues normally and c) how do we keep the virus in only in the tumor cells or make sure they only are able to work in tumor cells, and not normal cells. 
 
Believe me, just what you suggest is being considered.  I think it took a long time for anyone to answer this question because the answer is very very complex.  We have considered and are considering the above issues and a lot more, including manufacture, safety and getting drug approval for some of the ideas.  An example of a solution that has been found is a virus that only grows in cells with a certain mutation and *that* mutation is found in 80% of some tumors. When growing in cells with this mutation, it lyses or breaks the cells open.  Further, most of us have been exposed to this virus and have never been sick, nor does the virus grow in normal cells.  This is the perfect type of virus to be used as an oncolytic (tumor destroying) virus.  And it is…you can follow REOLYSIN going though its trials at the company’s web site if you like…http://www.oncolyticsbiotech.com/clinical.html   The clinical trial phase will take some time – your ideas are bang on, but they are going to take many years of testing – not just to be sure they work, but that they are safe to give to people.
 
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