An XMRV Derived Retroviral Vector as a Tool for Gene Transfer

[Jemal]

Published today:

Retroviral vectors are widely used tools for gene delivery and gene therapy. They are useful for gene expression studies and genetic manipulation in vitro and in vivo. Many retroviral vectors are derived from the mouse gammaretrovirus, murine leukemia virus (MLV). These vectors have been widely used in gene therapy clinical trials. XMRV, initially found in prostate cancer tissue, was the first human gammaretrovirus described. Findings: We developed a new retroviral vector based on XMRV called pXC. It was developed for gene transfer to human cells and is produced by transient cotransfection of LNCaP cells with pXC and XMRV-packaging plasmids. Conclusions: We demonstrated that pXC mediates expression of inserted transgenes in cell lines. This new vector will be a useful tool for gene transfer in human and non-human cell lines, including gene therapy studies.

http://www.virologyj.com/content/8/1/284/abstract

I am speechless at the moment. There is some weird stuff happening.

 

[Jemal]

From the PDF:

ACKNOWLEDGEMENTS
We thank UC-MEXUS CONACyT for support of this study with grant number CN08-229. We also thank Drs. Sandra and Francis Ruscetti, and Dr. John Elder, for providing primary antibodies.

(to be sure: I just thought it was interesting the Ruscettis were mentioned, I have no other motives)

 

[Rrrr]

From the PDF:

hi jemal or anyone,

can you tell us in lay terms what this means? i have no idea why you are speechless

rrrr

 

[Jemal]

I am a layman myself... but I will try and explain why I am speechless.
They are taking XMRV (which they describe as human gammaretrovirus) and they turn it into something that can be used to insert material in human genes. In the future gene therapy might be used to treat certain diseases. I am speechless, because everyone is saying XMRV is contamination, but it's a real virus and it can apparently infect cells well enough to make it interesting to consider as a vector for gene therapy.

To me it doesn't really rhyme with the whole "XMRV is contamination, nothing to see here" argument.

 

[kday]

That's one way to profit off this retrovirus!

I am aware that they use retroviral vectors for gene therapy, but that was still quite unexpected.

XMRV -> gene delivery didn't even cross my mind. Brilliant! Let's get in our lab and play with it since we are 110% sure it's completely benign.

Jokes aside - is this insanity?

 

[Jemal]

That's one way to profit off this retrovirus!

This was one of my thoughts as well...

 

[Spring]

So this study says XMRV can enter the human DNA...

Well if they are gonna use XMRV as a vector, we will see if those people develop ME/CFS. I only hope that's not the way how they are going to sort this out.
I think because of his reputation XMRV will never be used for this purpose.

 

[Jemal]

So this study says XMRV can enter the human DNA...

Well if they are gonna use XMRV as a vector, we will see if those people develop ME/CFS. I only hope that's not the way how they are going to sort this out.
I think because of his reputation XMRV will never be used for this purpose.

I am not an expert at gene therapy, but I think they change the viruses, so they don't run rampant and cause disease. They should target specific cells and insert material only there.

 

[alex3619]

Hi, typically a gene vector is heavily modified, but its modification depends on our current understanding - which is not good. However, I do worry that the propensity of MLVs to recombine might mean an otherwise benign vector could combine with another MLV to get ... what? Bye, Alex

 

[eric_s]

It really seems quite crazy. In the end they might use pXC to cure people from XRMV related diseases . I hope they know what they are playing with... I guess if the Ruscettis decided to help it's a good study.

 

[alex3619]

Hi eric_s, an XMRV vector would infect the same cell types as XMRV. So it could be used to treat prostate cancer perhaps, and if XMRV is indeed pathogenic, we could include an anti-XMRV factor in the vector. It could lead to interesting treatments - in ten or twenty years. I am of an age to look for my solutions elsewhere, but some might eventually benefit. Bye, Alex

 

[Jemal]

Hi eric_s, an XMRV vector would infect the same cell types as XMRV. So it could be used to treat prostate cancer perhaps, and if XMRV is indeed pathogenic, we could include an anti-XMRV factor in the vector. It could lead to interesting treatments - in ten or twenty years. I am of an age to look for my solutions elsewhere, but some might eventually benefit. Bye, Alex

Gene therapy still has many issues, so I am not even sure if it will be able to come to our aid in ten or twenty years. I don't want to wait ten or twenty years anyway...

 

[jenbooks]

They use HIV (lentivirus) to insert good genes into cells to help cure HIV someday.
Gene therapy has been making a lot of progress and they've used mouse leukemia viruses, HIV, and adenovirus, among others. They keep refining by taking out everything that could possibly be dangerous. What's left is a bit of virus called vector that can carry a good gene right into the cell where it's needed. It doesn't have the bad stuff anymore. They made some early mistakes--with adenovirus, they didn't take out enough of the inflammatory stuff. And with MLV's they cured SCIDS children but they have promoter sequences and they like to insert next to certain places like oncogenes. Lentivirus (like HIV) actually are safer and they take out most of the stuff.

 

[currer]

You might want to check out this paper.
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003144

A Natural human retrovirus effectively complements vectors based on murine leukemia virus
By Dong and Silverman.
They are concerned that "wild" xmrv in the population could recombine with replication incompetent genevectors to create a replication competent bioengineered virus.

And from what I've read over the past year it wont only be MLV viruses we have to be careful of. It looks to me that we have imported many animal retroviruses. Squirrel monkey retrovirus for one. So who can tell what is safe to release?

Frankly I am more afraid of medical bioengineering than germ warfare? Why? Because we believe it wont harm us so we are not suspicious of it. THere are massive amounts of money to be made in bioengineering - this is another reason why the XMRV finding is being resisted so much.