Engineered virus deletes genes -- Is this safe?

sjw's picture
Submitted by sjw on Sat, 2006-01-21 21:37

Engineered viruses that chop out genes? That sounds a little scary. Is anyone here familiar enough with the science to explain why this is perfectly safe? Like maybe they'd disabled the mice's immune system and that's why the virus could take hold? Or maybe the virus absolutely won't work unless injected into mice? Physical safety precautions against letting the virus out of the lab seem insufficient for something that could be so dangerous as the ability to disable genes.

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"in retrospect, chopping a

Robert's picture

"in retrospect, chopping a gene out of DNA in vivo seems quite beyond us technically"

In an adult multi-celled organism it isn't totally beyond us. It really depends on what organism you are talking about and which gene you intend to turn off.

You have to remember that although every cell in your body carries your entire individual genome, most of that genome is turned off in any one cell. Only those genes relevant to the tissue/temporal and spatial position of the cell are turned on in a multicellular organism.

So biology has done most of the job for us. The only problem is that targeting the deletion tool to a set of cells in a particular tissue is difficult. As I said, this isn't my field, but I believe we aren't too far away from being able to develop corrective gene therapies based around limited cutting & pasting of genes.

For instance, I can envision (just don't ask me to do it) that you could knock out or replace a gene expressed in the bone marrow of a leukemia patient.

You'd just have to get stem-cells from the subject and do the cut and paste job on them. The right sort of stem cells are found in small numbers in the after-birth an in the umbilical chord. I believe you can ask the hospital to save and freeze these for your child right now.

According to a book I've been reading (How Cancer Works) such stem cells, when transplanted into a Leukemia patient should, over time regenerate bone marrow killed off (because it is cancerous) by chemo- and radiation therapy.

So why would you KO a gene in stem-cells you want to transplant into a cancer patient? Perhaps because the cancer is of an inherited type and transplanting untreated stem-cells would just allow the problem to repeat itself.

Yes, this is still science fiction. How long for is the question, I'm betting that such therapies should arrive in my lifetime.

[How Cancer Works by Lauren Sompayrac PhD. It is very well written and very good value at ~$20 2nd hand from Amazon. Just the thing for the knowledgeable layman who's interested in understanding cancer better.]

Thanks guys

sjw's picture

That makes a lot more sense, both the idea of viral vectors and the RNA silencing (in retrospect, chopping a gene out of DNA in vivo seems quite beyond us technically).

From the abstract:"Here,

Robert's picture

From the abstract:

"Here, using a viral vector to temporally control a focal deletion of the NR1 gene"

Sounds to me like a silencing RNA experiment. In these experiments the viral vector is the "drug capsule" that delivers a dose of RNA or morpholino sequence to bind to the RNA transcribed from the gene. The idea is to prevent the translation of the RNA, causing a temporary reduction (how much of a reduction depends on how lucky/good the scientist is) in the gene's product (protein/peptide etc.)

We can actually cause the deletion of genes, but - in animals (plants, fungi & bacteria are different again) - you'd have to delete the gene in the embryo, because the embryo contains only one set of the DNA. And even then you'd have to know where the gene was and how many copies of it there were (there should be a minimum of two in diploid organisms - assuming the gene isn't on the determining sex chromosome and blah blah blah.)

The problem here is that the embryo may not grow properly (or at all) without that gene. So this siRNA technology makes it easier - in some cases - to study the effects of turning off or reducing the "production from a gene."

This isn't my field, so there are a couple of things I'm fuzzy on. How does the researcher get around the immune systems in higher-order animal subjects? Is the viral vector based on a "stealthy virus" or is the host from a immune-deficient line of research animals?

What proportion of cells, in general, need to have this silencing nucleotide before you see a change in the phenotype?

Remember an adult animal is a multi-cellular organism - every cell in that target tissue has a copy(Drunk of the gene you want to turn off.

If an expert can come on and answer my questions and correct any mistakes I've made, I'd be grateful!!


Viral vectors can't replicate

Phil Howison's picture

Chopping out genes sounds dangerous, but the main danger from viruses is that they take over cells and use them to replicate. A virus reproduces by destroying the host cell to produce many more copies of itself. If it is modified to deliver a gene (or a DNA sequence that disables a gene) there is no danger.

Also, some vectors have a temporary effect - they deliver sequences that aren't replicated along with the host cell, so regular doses are necessary. That could act as another safeguard.

The abstract of the paper is

Hong's picture

The abstract of the paper is here:

I am not able to access the full paper in J. Neurosci. from home. In the abstract, it is said that they used "a viral vector". Now, a viral vector is a very different thing from a viable virus. It is a genetic manipulation tool researches use all the time. It is usually constructed in such a way that unless we specifically induced it, it dosen't really do anything. And it is usually designed to carry out only a single specific function. Perhaps Marcus would know more about this. I am more familiar with bacterial vectors.

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