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Zinc Finger Proteins Put Personalized HIV Therapy Within Reach

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oh-no:
There was another similar study with HIV immune stem cells from Canada.
The method was called OZ1.

http://www.catie.ca/en/treatmentupdate/treatmentupdate-172/anti-hiv-agents/clinical-trial-gene-therapy-hiv

The scientists took cells from patients made the cells resistant to HIV and infused them back.

Results:
Four weeks after infusion, technicians detected HIV-resistant cells from blood cells in 94% of people in the OZ1 group. One year after the infusion, this figure fell to 12% and two years after the infusion it fell to 7%.
No statistical significance of viral load or cell count.

Stem cells suppose to reproduce themself and produce HIV resistant T-cells.

But the majority (90%) of stem cells sits in the marrow bone. So the marrow bone is the main producer of blood cells and lymphocytes. That is why blood infusion cant repeat the marrow bone transplantation experience of Berlin patient.

In addition to marrow bone transplantation Berlin patient is on the immune suppress medication which suppress HIV. It is more dangerous than arvt. He also developed graft-versus-host disease very strong immune reaction when donor cells attack patient's HIV infected cells.

I'm sure scientists and direction from Sangamo have basic knowledge of human immunity system, they also know about similar OZ1 trials which did not succeed. So they can predict results.

Of course this doesn't mean they should stop experiment. It is a step forward for the science and medicine. With new knowledge some day the new approach will be discovered. But not in the foreseeable future, even for those who is not infected with HIV.
That is why they do their trials so slowly. Time and loud promises brings money for them.

Tadeys:
Oh no: this is the reference to what you wrote: http://www.catie.ca/en/treatmentupdate/treatmentupdate-172/anti-hiv-agents/clinical-trial-gene-therapy-hiv

Sangamo is light years ahead of OZ1. Calimmune is even way more avanced then Sangamo. City of Hope should have something soon way more avanced then Calimmune...see a pattern? :)

Cheers

oh-no:
All studies just use different methods to make cells resistant to HIV.
This goal is already archived. But this doesn't brings right result for the human body: persistent presence of modified cells, significant VL decline and cell count rise.

Canadian scientists point on future goals.
Gene therapy experiments need to find ways to do the following:
get more CD34+ stem cells to take hold in the bone marrow
prolong the life of CD4+ cells containing gene therapy
demonstrate significant anti-HIV activity (lower VL)

Stem cells multiplies and live longer in bone marrow.
So the goal is to deliver them here. Theoretically it could be the process similar to transplantation, but with autologous cells. In this case there is no need to destroy patient's own immune system with chemotherapy. First bone marrow is took from the bone than modified and than injected back. But today nobody even talk about this.

They move with little steps, when the whole picture is already visible. It is like to produce phone first with 500MB memory than 1GB than 2GB when technically it is already possible to produce phone with 2GB.


However I agree there is always should be a place for the hope.

Hoyland:

--- Quote ---All studies just use different methods to make cells resistant to HIV.
This goal is already archived. But this doesn't brings right result for the human body: persistent presence of modified cells, significant VL decline and cell count rise.
--- End quote ---

Actually the fact that different methods are used means that different outcomes can be achieved. The study referred to used RNA ribozyme to treat the stem cells. Many scientist in the field no longer believe that using a ribozyme on its own can provide the long term benefits required to produce a HIV cure. Both the Calimmune and the CoH techniques involve turning off a gene that produces the CCR5 receptor, which is essential to the entry of HIV into human cells. (CoH additionally use a ribozyme as part of their treatment.) They do this through modifying cell DNA, which means that the modification is replicated each time the cell divides. The potential is for such treatments to last a lifetime, not only halting a current infections (the virus has nowhere to go)  but also preventing future infections. 

There is still a problem of transfection (as was shown in the first CoH trial) but slowly the rate of transfection has been improving. The UC Davis team achieved twice the transfection rate in mice than the original CoH pre-clinical work. The CoH are now working on improving transfection and will conduct a Pll trail when they have completed their current investigations.

Hopefully, it won't be too long before we see some data on transfection rates from the current Calimmune trial. If enough cells can be modified, there is no reason to doubt that those treated will, at some point in the future, produce enough modified cells to rid the body of the virus.

Note: One of the patients in the CoH trail in 2010 is still producing increasing levels of the therapeutic cell even though the original transfection rate was very low. See video.  http://www.youtube.com/watch?v=9XqJyYrYgwU

Hoyland:
Sorry, I forgot to mention that Geoff Symonds, one of the co-authors of the paper, worked for J&J at the time the referenced paper was produced and he is now Calimmune's Chief Scientific Officer.

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