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Author Topic: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach  (Read 151718 times)

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Offline J220

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From http://www.sciencedaily.com/releases/2008/06/080630093611.htm :

ScienceDaily (June 30, 2008) — Researchers at the University of Pennsylvania School of Medicine and collaborators are using minute, naturally occurring proteins called zinc fingers to engineer T cells to one day treat AIDS in humans.

"By inducing mutations in the CCR5 gene using zinc finger proteins, we've reduced the expression of CCR5 surface proteins on T cells, which is necessary for the AIDS virus to enter these immune system cells," explains first author Elena Perez, MD, PhD, Assistant Professor of Pediatrics at Penn. "This approach stops the AIDS virus from entering the T cells because it now has an introduced error into the CCR5 gene."

Some people are born with a mutation on their CCR5 gene and therefore do not have a working CCR5 receptor on the surface of their T cells. These rare individuals are immune to HIV infection and seemingly are not affected by the non-functional CCR5 protein. The zinc finger approach aims to mimic this natural immunity.

Perez performed the research while a postdoctoral fellow in the lab of senior author Carl June, MD, Director of Translational Medicine at the Abramson Family Cancer Research Institute, and a Professor of Pathology and Laboratory Medicine at Penn. Perez is also an attending physician with the Children's Hospital of Philadelphia in the Division of Allergy and Immunology.

Normally, zinc fingers bind to different bases in the DNA sequence to regulate the activity of genes. The zinc fingers used in this experiment were designed to bind to specific DNA sequences in the CCR5 gene. The CCR5 protein is one of the two cell-surface receptors needed for HIV to gain entry into a T cell in order to replicate.

In this study, the zinc finger protein brings a DNA enzyme to the CCR5 gene to cut a portion of its sequence, but due to the repair process a new mutation arises in the CCR5 protein, rendering it non-functional. Without a functional CCR5 protein on the cell's surface, HIV cannot enter, presumably leading to resistance to HIV infection.

The researchers demonstrated this process in cell culture and in a mouse model. For the animal part of the study, the investigators used healthy human CD4 T cells and added DNA that expresses the zinc fingers, which modifies the CCR5 co-receptor. They grew the engineered cells in tissue culture flasks and transferred them into immune-deficient mice infected with HIV. "We followed them over time and showed that those mice that received the zinc-finger-treated cells showed less viral load than controls and improved CD4 counts," says Perez.

The researchers are planning a clinical trial in humans in which T cells from HIV patients would have their CCR5 gene deliberately knocked out. These modified T cells could then be infused back into the patients to re-establish their immune system and decrease their viral load.

Dr. Perez and Dr. June have no financial relationship with Sangamo.
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline NYCguy

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #1 on: July 01, 2008, 06:50:03 PM »
Sangamo previously claimed that there would be a trial in 2007.  Let's hope they start one soon, rather than sending out more press releases.
11/9/06 = #$%^&!
sometime early Dec 2006:
CD4 530 20%/VL >250,000 (&*$$%!!)
started Reyataz300mg/Norvir/Truvada 12-27-06.
1/30/07 CD4 540 30%/VL <400
4/07 CD4 600+ 33%/VL <50
6/9/07 CD4 720 37%/VL <50
10/15/07 CD4 891 (!) %? VL <50
1/2010 CD4 599 (37%) VL<50 (drop due to acute HCV)
9/2010 - looks like HCV is gone for good! And I'm finally drinking again, thank GOD
2013 - considering a switch to Stribild. but I love my Kidneys (but I hate farting all the time!)...
June 2013 - switched to Stribild.  so far so good...

Offline bimazek

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #2 on: July 02, 2008, 05:24:09 PM »
http://www.sciencenews.org/view/generic/id/33799/title/HIV_knockout

a little more science detail on this discovery if you are into that

my hope is that in 5 years we will all have some non toxic treatment

haart may still be arround in some cases like mutated virus that is resistant

maybe 7 years is my hope

Offline bimazek

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #3 on: July 04, 2008, 01:52:35 PM »
this looks like it could be a major major breakthrough - lets hope that there rapid movement forward - lot of detailed science here

Find a specific gene and then  turn it on or off.
ZFP-Therapeutics are designed to activate or repress specific genes relevant to human diseases. More...
http://www.sangamo.com/index.php

TEN DIAGRAMS TO EXPLAIN HOW IT WORKS
http://www.sangamo.com/tech/our_tech_ex.html
 Engineering Transcription Factors to Regulate Genes
Transcription factors are naturally occurring proteins that function within the nucleus of a cell to regulate gene expression. Transcription factors function by binding to specific sites on DNA and causing nearby genes to be turned on or off. (fig. A)

PDF on how they have had success with AIDS
http://files.shareholder.com/downloads/SGMO/351574819x0x209704/40e1ddfe-7186-4503-8904-8751b5b3fe55/SGMO_News_2008_6_30_General_Releases.pdf

www.sangamo.com  is the company that invented all this!!


details on technology of ZPT
http://www.sangamo.com/tech/tech.html
how USLCA is using sagamo ZPT tech to treat aids
http://www.sangamo.com/human/human_thera_overview.html#HIV



Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS)
HIV infection results in the death of immune system cells and thus leads to AIDS, a condition in which the body’s immune system is depleted to such a degree that the patient is unable to fight off common infections and ultimately  succumbs to opportunistic infections or cancers.  CCR5 is the co-receptor for HIV entry into T-cells and without CCR5 expressed on their surface, HIV cannot infect these cells.  A population of individuals has been identified that is immune to HIV infection, despite multiple exposures to the virus. They have a natural mutation, CCR?532, that results in the expression of a shortened, non-functional CCR5 protein. This mutation appears to have no observable deleterious effect on the growth or survival or these individuals. We are using our ZFN-mediated gene disruption technology to disrupt the CCR5 gene in cells of a patient’s immune system to make these cells permanently resistant to HIV infection.  The aim is to provide a population of HIV-resistant cells that can fight opportunistic infections. In collaboration with scientists at the University of Pennsylvania and the University of Los Angeles California, UCLA, we are pursuing both ex- and in vivo approaches in T-cells and hematopoietic. Sangamo anticipates filing an IND for this therapeutic in 2008.

cute guys who helped invent this technology
http://www.sangamo.com/discovery/discovery.html


http://www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt1410.html
Article abstract
Nature Biotechnology
Published online: 29 June 2008 | doi:10.1038/nbt1410
Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
Abstract
Homozygosity for the naturally occurring Delta32 deletion in the HIV co-receptor CCR5 confers resistance to HIV-1 infection. We generated an HIV-resistant genotype de novo using engineered zinc-finger nucleases (ZFNs) to disrupt endogenous CCR5. Transient expression of CCR5 ZFNs permanently and specifically disrupted approx50% of CCR5 alleles in a pool of primary human CD4+ T cells. Genetic disruption of CCR5 provided robust, stable and heritable protection against HIV-1 infection in vitro and in vivo in a NOG model of HIV infection. HIV-1-infected mice engrafted with ZFN-modified CD4+ T cells had lower viral loads and higher CD4+ T-cell counts than mice engrafted with wild-type CD4+ T cells, consistent with the potential to reconstitute immune function in individuals with HIV/AIDS by maintenance of an HIV-resistant CD4+ T-cell population. Thus adoptive transfer of ex vivo expanded CCR5 ZFN–modified autologous CD4+ T cells in HIV patients is an attractive approach for the treatment of HIV-1 infection.


http://investor.sangamo.com/stockquote.cfm?benchmark1=&Event1=&DisplayType=Area&Period=560&CustomFromDate=6%2F20%2F2004&CustomToDate=10%2F30%2F2004

Offline John2038

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #4 on: January 31, 2009, 06:03:39 PM »
Milestone Achieved A Year Ahead of Schedule (Jan 12, 2009)

Sangamo BioSciences, Inc. (Nasdaq: SGMO) today announced it has reached a major production capacity milestone as part of its agreement with Sigma-Aldrich Corporation (Nasdaq: SIAL) to commercialize zinc finger nuclease reagents (ZFNs) for research applications. The milestone triggers a payment of $1.0 million to Sangamo.

Full story

More about ZFN and Video

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #5 on: June 05, 2009, 03:34:37 PM »

The researchers are planning a clinical trial in humans in which T cells from HIV patients would have their CCR5 gene deliberately knocked out. These modified T cells could then be infused back into the patients to re-establish their immune system and decrease their viral load.


Update, this article says they are starting to test this on humans already:

Trial Begins for HIV Gene Therapy
By Aaron Rowe   February 3, 2009  |  4:00 am  |  Categories: Biotech, Medicine & Medical Procedures

Gene therapy that could immunize people against the most common type of HIV is ready to be tested on humans.

Recruiting for the trial began Tuesday, and the first people to receive the experimental treatment will be HIV patients with drug-resistance problems.

"We do have good treatments for HIV. That has been one of the most successful stories of the last 20 years in medicine," said Pablo Tebas, an infectious disease expert at the University of Pennsylvania.

"However, over time, if the medications are not taken properly, individuals develop resistance to the HIV treatments, so they tend to have more limited therapeutic options."

Since the discovery that a small portion of people who are exposed to HIV do not get infected, scientists have been working to discover the secret to those people’s resistance and how to make others resistant as well.

It turns out that most people have a gene called CCR5, which makes them vulnerable to HIV infections. The naturally resistant people have mutant CCR5 genes that inhibit HIV.

Previously, scientists found that by cutting the CCR5 gene out of white blood cells involved in the immune response known as T-cells, they could protect a tube full of human cells from the virus. The gene editing technique relies on proteins called zinc finger nucleases that can delete any gene from a living cell.

In theory, zinc finger nucleases could give that immunity to anyone.

The procedure is simple: Take some healthy T-cells out of an HIV patient, clip out their CCR5 genes, grow more of these clipped T-cells in a dish, and then put them back in the patient.

"In this first study we will re-infuse approximately 10 billion of these cells back into the participants, and we will see if it is safe and if those cells inhibit HIV replication in vivo," said Tebas. "We know they do in the test tube."

LINK:

http://www.wired.com/wiredscience/2009/02/hivtreatment/

CLINICAL TRIAL LINK:

http://clinicaltrials.gov/ct2/show/NCT00842634
« Last Edit: June 06, 2009, 03:10:10 PM by Inchlingblue »

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #6 on: June 06, 2009, 03:33:34 PM »
Can you feel the love?

[attachment deleted by admin]
Beware Romanians bearing strange gifts

Offline dadx4

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #7 on: June 29, 2009, 10:23:29 AM »
Are any of you in this trial?  How's it going if you are participating, I know they are still recruiting.  They are only taking 12 patients to start though. 
« Last Edit: June 29, 2009, 02:51:16 PM by dadx4 »

Offline brazilianman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #8 on: July 06, 2009, 08:35:11 PM »
hello, I'm from Brazil and I like the forum on anti-ps is a good theory. I would like to know what the strength of the forum to ask for drug companies on research? much is spoken but not proven. vrx496? pro 140? Anybody know about this? sorry bad English.


Antibody specificities associated with neutralization breadth in plasma from HIV-1 subtype C infected blood donors

Offline brazilianman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #9 on: August 23, 2009, 05:43:57 PM »
 ???  any news? Zinc finger where? the study is stopped or moving?   ???

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #10 on: August 23, 2009, 06:35:58 PM »
???  any news? Zinc finger where? the study is stopped or moving?   ???

The trial started February 2009, it's too soon to know anything.

Estimated Study Completion Date:   March 2011

Offline brazilianman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #11 on: August 24, 2009, 08:41:18 AM »
Inch.

seems not yet begun. they are recruiting candidates. this treatment model can work.

this method is not like the dr. hutter?
somebody registered?

I'm optimistic. ;D

http://clinicaltrials.gov/ct2/show/NCT00842634

Offline dadx4

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #12 on: August 24, 2009, 09:57:50 PM »
I think they have all of the candidates now and they may have an update December of next year.   Could you imagine if this actually works...

Offline Carlos3000

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atripla

09/10      cd4 564  Und  30 %

Offline xman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #14 on: September 16, 2009, 05:13:14 PM »
i'm a bit concerned about the safety of this approach. even if we know that persons lack this gene naturally we still don't know if they have another protein or enzyme which replaces its function. if you simply turn off the ccr5 coreceptor we don't know if this could interact negatively in the normal immune function. i guess this is a reason why the first clinical phases are so long.
sign the petition launched by the aids policy project addressed to the nih aimed to increase the money needed to find the cure:

http://www.aidspolicyproject.org/petition_for_the_nih

we can make a difference and we need to fight. please support them! it doesn't cost you anything. they need it now more than ever!

Offline marius68

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #15 on: September 23, 2009, 08:13:12 AM »
Zinc Finger therapy is progressing!! Most likely it means results from current trial are good!!

http://investor.sangamo.com/releasedetail.cfm?ReleaseID=410950


Sangamo BioSciences Announces Plans to Initiate a Second Clinical Trial of CCR5-ZFP Therapeutic to Treat HIV/AIDS

Expansion of Program Will Test Repeat Dosing Protocol of SB-728-T

RICHMOND, Calif., Sept 23, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today that the US Food and Drug Administration (FDA) has reviewed and accepted an Investigational New Drug (IND) application to initiate an open-label, repeat-dosing Phase 1 clinical trial (SB-728-T-902) of the company's ZFN-based therapeutic, SB-728-T. A single dose Phase 1 clinical study of SB-728-T was initiated in February 2009 and is ongoing at the University of Pennsylvania. Both Phase 1 studies are designed primarily to evaluate the safety and tolerability of this ZFP Therapeutic(TM) approach, however subjects' CD4 T-cell counts, levels of CCR5-modified T-cells and viral burden will also be monitored.

"Opening a second Phase 1 clinical trial of this exciting new approach to HIV/AIDS treatment enables us to expedite clinical and commercial development of SB-728-T. We are very pleased with the FDA's decision enabling us to expand this program and move forward quickly with a repeat-dosing trial," said Dale Ando, M.D., Sangamo's chief medical officer and vice president of therapeutic development.

"The best approach to controlling HIV is by preventing infection of cells in the first place. Since 1996, when CCR5 was validated as a target for HIV therapy, the goal has been to recapitulate the naturally-occurring protection against viral infection exhibited by individuals who have the CCR5-delta32 mutation. We have the ability to disrupt the CCR5 gene and make human T-cells resistant to infection by CCR5-specific strains of HIV. In this trial we will be evaluating SB-728-T in subjects that have well-controlled levels of virus but have sub-optimal recovery of CD-4+ T-cell counts despite long-term triple drug therapy. This group represents approximately thirty percent of all HIV-infected patients in the US and may particularly benefit from this novel T-cell ZFP Therapeutic approach."

Based on Sangamo's zinc finger DNA-binding protein nuclease (ZFN) technology, SB-728-T has been shown in an animal model of HIV infection to lead to an increase in CD4+ T-cell counts, a reduction in viral load and expansion of CCR5-modified T-cells, suggesting resistance to HIV.

"Although it is still early days, we are encouraged by what we have seen in pre-clinical experiments and in the ongoing Phase 1 clinical trial that is being run by collaborators at the University of Pennsylvania," commented Edward Lanphier, Sangamo's president and CEO. "This new study is another important step in our mission to establish ZFP Therapeutics as a major new therapeutic product development platform. Moving our first ZFN technology-based product efficiently through the development process is vital to that goal. SB-728-T represents a new treatment paradigm for the treatment of HIV and we are very excited to expand its clinical development."

CCR5 is a co-receptor that enables HIV to enter and infect cells of the immune system. It has been observed that individuals carrying a natural mutation of their CCR5 gene, CCR5-delta32, are highly resistant to infection by HIV, despite high-risk behaviors. These individuals, lacking a functional CCR5 (approximately 1-2% of the general population), are otherwise immunologically "normal". A variety of small molecule and antibody antagonists of CCR5 binding have been tested and developed as potential therapeutic agents for the treatment of HIV infection. In addition, there is a recent report of a patient who had both HIV infection and leukemia and received a bone marrow transplant from a donor carrying the CCR5 mutation. After the successful bone marrow transplant, HIV treatment was discontinued and the virus could not be found in the circulating blood several months after the procedure. Sangamo's ZFNs are designed to modify the DNA sequence encoding CCR5. This modification can occur directly in T-cells with only a brief exposure to the ZFNs. Once the modification is made to the T-cell's CCR5 gene it is permanently disrupted.

About the SB-728-T Clinical Trial (SB-728-T-902)

The study is an open-label Phase 1 clinical trial to evaluate the safety and tolerability of repeat infusions of autologous (a patient's own) CD4+ T cells genetically modified at the CCR5 gene by CCR5-specific ZFNs (SB-728-T). The trial will enroll a total of nine HIV infected subjects on long-term, stable anti-retroviral therapy whose virus is undetectable in their blood by conventional methods but who have exhibited suboptimal CD4+ T-cell gains. The trial will have three dosing cohorts. The first cohort to be treated will receive a single dose, the second cohort, two doses at fourteen day intervals and the third cohort, three doses at fourteen day intervals. The subjects in each cohort will be treated sequentially and monitored for 2 months after their last treatment before an additional subject is treated. After this period of evaluation and monitoring has passed successfully, the next cohort will be treated, again sequentially. Subjects will remain on their existing antiviral therapy while receiving treatment with SB-728-T. The primary objective of the study is to evaluate the safety and tolerability of SB-728-T. In addition to safety monitoring, data will be collected on the expansion and persistence of ZFN-modified cells, CD4+ cell counts and viral load.

Preclinical Data

Preclinical data on SB-728-T were published in the journal Nature Biotechnology (Perez E. E. et al., Nat Biotechnol. 2008 Jul; 26(7):808-16.) and presented at the joint meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the Infectious Diseases Society of America (IDSA) in Washington, DC in October 2008. The results demonstrate that a one-time exposure to CCR5-specific ZFNs resulted in the generation of an HIV-resistant population of human primary T-cells by the permanent genetic modification of the CCR5 gene. These ZFN-modified CD4 T-cells expanded stably in HIV-infected cultures for several weeks and behaved identically to untreated T-cells except that they were resistant to infection by HIV. ZFN treated primary CD4 T-cells and transformed CD4 cell lines resisted infection with R5-tropic HIV (virus that uses the CCR5 co-receptor to enter cells), resulting in enrichment of ZFN-generated CCR5-disrupted cells in the population upon long-term exposure to virus (>50 days). Importantly, in the presence of HIV, ZFN-modified CD4 T-cells also preferentially expanded in a mouse model. The modified cells were infused into mice that lack a normal immune system and thus do not reject human cells. After 33 days, the mice were sacrificed and analyzed for the presence of ZFN-modified cells. Researchers determined that ZFN-modified cells engrafted normally in the mouse and that the proportion of modified cells present at the end of the experiment was greater than two to three fold higher in mice in the presence of HIV infection (p=0.008). In additional experiments, it was determined that 50 days after infection, mice given the ZFN-modified cells had increased numbers of CD4 cells and a statistically significant reduction in viral load in their peripheral blood (P<0.001) compared to mice given control cells. These data suggest that, in the presence of HIV, the ZFN-modified cells have a selective advantage allowing them to evade infection and destruction.

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #16 on: September 23, 2009, 11:08:36 AM »
I have lots of faith in zinc finger and other technologies that knock out CCR5 but I was reading the article on thebody.com with Dr. Jeffrey Laurence, updating the status of the patient in Berlin who was cured of both HIV and Leukemia (talk about hitting the jackpot) and he said existing technologies are not able to knock out CCR5 100% which is what is needed. I actually thought zinc finger was able to knock it out 100% in the cells extracted from a particular patient so this is surprising. This is what he said about current technologies for mutating CCR5 (what he describes in the second paragraph is what I thought ZFN does, at least that's how it's been described in the literature from Sangamo):

The ideas are out there on how to do it. Basically, what you need to do is mutate this gene in every single cell that you're going to transplant into a person. What if we just took the person's own cells, or that of the next available donor that walks in the door who happens not to have the CCR5 mutation -- as statistically they won't -- and genetically give them the mutation?

Can we knock out the gene for CCR5? That's called genetic engineering. We're really good at doing genetic engineering in one cell. But the average person getting transplanted is getting a few billion cells, and we have to guarantee that 100.0 percent of those few billion cells all have their genes modified. We could take a few hundred or a few thousand cells, make certain that every single one of them has that gene modified, and then grow them into billions of cells that we can inject back into the patient, but we don't know how to do that.

Some of the physician scientists that I mentioned that I invited to our think tank in September are working on that. They're working on it in mice, and they're working on it in monkeys. With current technology, in a monkey or in a mouse or in a test tube, you can knock out the CCR5 gene in maybe as much as 90 percent of the cells. But we need 100.0 percent of cells to be CCR5 negative, because if even one little cell has the capacity to be infected with HIV and it starts multiplying in your body, that's the end of your cure.

So I think it's partly a technology problem, and that's where research comes in. We know what we need to knock out: CCR5. We have people looking, as I mentioned earlier, for other things that might account for other people being resistant to getting infected with HIV. If we find those changes, we'll have other targets to knock out.

All we need to do now is come up with better technologies than the small interfering RNAs, the zinc finger nucleases, the oligonucleotide reductases, the ribozymes and so forth. All these words for ways that we knock stuff out to get us closer to 100 percent. That's where research is so important.

"This is an important area of research that needs multiple people looking at it from multiple different angles because none of those technologies are 100 percent accurate in knocking a single gene out in 100 percent of the cells."

I have a lot of faith in this kind of research. It's going to enable us to just take cells from the first acceptable donor, as if the patient didn't have HIV, knock out that gene and give it to the patient, and replicate what happened in Berlin.


LINK:

http://www.thebody.com/content/art53624.html
« Last Edit: September 23, 2009, 11:23:34 AM by Inchlingblue »

Offline brazilianman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #17 on: September 23, 2009, 06:50:55 PM »
Inch
I see zinc finger with other therapies. If the project goes well Adaptimmune can join them.
One is a hunt for hiv other protects the cell and the hiv

;D

Bman

Offline Cosmicdancer

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #18 on: September 23, 2009, 08:22:08 PM »
Even if you can't modify 100% of t-cells with the CCR5 mutation, it seems that this approach would have a lot of therapeutic value.  Afterall long-term non-progressors still have varying levels of HIV since they are not able to eradicate it.  And if HIV continues to kill off the non-mutated t-cells, while the modified ones are repopulating the CD4s, won't they eventually comprise most if not all of the t-cells in a treated individual?  Maybe I'm not understanding how this works, but if this therapy can offer the possibility of many years off meds, I'd welcome it as a major breakthrough. 
Summer, 2007 - &$#@?
November, 2007 - Tested poz, 300,000 vl, 560 cd4
Feb, 2008 - 57,000 vl, 520 cd4, started Atripla
June, 2008 - undetectable, 612 cd4
January, 2009 - undetectable, 670 cd4
May, 2009 - undetectable, 593 cd4
Sept, 2009 - 83 vl, 763 cd4, 34%
Dec, 2009 - undetectable, 889 cd4, 32%
April, 2010 - undetectable, 860 cd4, 31%
October, 2010 - undetectable, 800 cd4, 38%
April, 2011 - undetectable, t-cell test not done
October, 2011 - undetectable
April, 2012 - undetectable, 850 cd4, 39%
November, 2012 - undetectable, 901 cd4, 41%
April, 2013 - undetectable, 846 cd4, 36%
October, 2013 - undetectable
May, 2014 - undetectable, 784 cd4, 48%

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #19 on: September 24, 2009, 01:23:20 AM »
brazilianman & cosmicdancer, you both make very good points.

Offline hahaha

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #20 on: September 24, 2009, 02:15:48 AM »
How come nobody mentioned about CXCR4 issue in zing finger treatment? Does it matter still?
Aug 9, 2006 Get infected in Japan #$%^*
Oct 2006 CD4 239
Nov 2006 CD4 299 VL 60,000
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Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #21 on: September 24, 2009, 11:26:31 AM »
How come nobody mentioned about CXCR4 issue in zing finger treatment? Does it matter still?

There are other therapies looking at blocking entry through CXCR4 but as far as I am aware, zinc finger does not work with CXCR4.

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #22 on: September 24, 2009, 01:45:29 PM »
How come nobody mentioned about CXCR4 issue in zing finger treatment? Does it matter still?

Sangamo (the Zinc Finger people) have a CXCR4 project in preclinical.
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Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #23 on: September 24, 2009, 02:42:41 PM »
Sangamo (the Zinc Finger people) have a CXCR4 project in preclinical.

I know there are CXCR4 projects but I didn't know there were any from Sangamo using ZFN, that's awesome. I'll go Google it now ;)

EDITED TO ADD: Freewillie, I found an entry inhibitor called AMD-8445, which I guess is it but I couldn't find much. Do you have any more info on it?
« Last Edit: September 24, 2009, 02:49:53 PM by Inchlingblue »

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #24 on: September 24, 2009, 03:05:26 PM »
EDITED TO ADD: Freewillie, I found an entry inhibitor called AMD-8445, which I guess is it but I couldn't find much. Do you have any more info on it?

Here's a link to a slide from a recent Sangamo presentation which mentions it.  Note that it's the last entry at the bottom.  

http://cc.talkpoint.com/ubsx001/092109a_ke/content/116_C8PIWBN/slides/Slide14.png

Their CXCR4 project was also mentioned earlier this week in an investor conference call.

Rock on with Zinc Finger!!
« Last Edit: September 26, 2009, 10:50:36 AM by freewillie99 »
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Offline marius68

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #25 on: September 28, 2009, 07:46:07 PM »
Sangamo will be updating their ZF program on October, 5. They seem to be very active lately!!! Can't wait for the end of the clinical trials!!

Sangamo BioSciences Announces Presentation at the JMP Securities Healthcare Conference

RICHMOND, Calif., Sept 28, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today that Edward Lanphier, Sangamo's president and CEO, will provide an update on the progress of Sangamo's ZFP Therapeutic(TM) development programs and an overview of the company's business strategy at 9:30 am ET on Monday, October 5, 2009 at the Fourth Annual JMP Securities Healthcare Focus Conference which will be held in New York City.

The presentation will be webcast live and may be accessed via a link on the Sangamo BioSciences website in the Investor Relations section http://investor.sangamo.com/index.cfm under Events and Presentations. The presentation will be archived on the Sangamo website for two weeks after the event.

Offline marius68

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #26 on: September 28, 2009, 10:00:08 PM »

An interesting study was recently published on the outcome of gene therapy. From the abstract: "The modelling indicates a single infusion of HSC cell-delivered gene therapy can impact on HIV viral load and CD4 T-lymphocyte count. Given that gene therapy avoids the complications associated with HAART, there is significant potential for this approach in the treatment of HIV."

http://www.ncbi.nlm.nih.gov/pubmed/19777528?ordinalpos=38&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum


Through mathematical modeling anti-HIV gene therapy was analyzed. in particular the OZ1 ribozyme of Dr. Mitsuyasu. This was  discussed before (link following) but I decided to include under the ZFT topic since there seems to be a lot of activity from sangamo.

http://forums.poz.com/index.php?topic=25779.0

http://www.ncbi.nlm.nih.gov/pubmed/19219022?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=3&log$=relatedarticles&logdbfrom=pubmed


Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #27 on: October 28, 2009, 05:45:14 PM »
Sangamo just got a big grant to continue exploring ZFN. This particular grant is for silencing CCR5 in patients with AIDS-related lymphoma but the clinical trial that is currently ongoing from Sangamo (using ZFN) is for patients with HIV with no other complications.


Sangamo BioSciences Research Collaborators Awarded Grant From California Institute for Regenerative Medicine to Develop Zinc Finger Nuclease-Based Stem Cell Therapy for HIV/AIDS

$14.5 million award to bring ZFP HIV therapy to the clinic

RICHMOND, Calif, Oct 28, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today that the California Institute for Regenerative Medicine (CIRM) has granted a $14.5 million Disease Team Research Award to develop an AIDS-related lymphoma therapy based on the application of its zinc finger nuclease (ZFN) gene-editing technology in stem cells. The four year grant supports an innovative research project conducted by a multidisciplinary team of investigators led by John Zaia, M.D. the Aaron D. and Edith Miller Chair in Gene Therapy and chair of virology, City of Hope. The grant application entitled "Zinc Finger Nuclease-Based Stem Cell Therapy for AIDS" won the highest score of all grants CIRM received in this 1st round of Disease Team Research Award funding.

"Sangamo scientists have developed a ZFN-mediated gene-editing technology that has been demonstrated to make hematopoietic stem cells and mature immune system cells resistant to HIV infection," said Dr. Zaia. "This will be the first test of whether hematopoietic stem cells made HIV resistant using Sangamo's technology can correct the disease. If successful, our work could open the door to ZFN-based cell therapies for other important diseases."

Patients homozygous for a natural mutation (the delta-32 mutation) in the CCR5 gene are resistant to HIV infection by blocking the ability of the virus to enter a cell. Building on this observation, a study published in the New England Journal of Medicine in 2009 reported a potential "cure" in an AIDS patient with leukemia after receiving a bone marrow transplant from a "matched" donor with this delta-32 CCR5 mutation. This approach transferred the hematopoietic stem cells (HSC) residing in the bone marrow from the delta-32 donor, and provided a self-renewable and lifelong source of HIV-resistant immune cells. After transplantation, this patient was able to discontinue all anti-HIV drug treatments, CD4 counts increased, and the viral load dropped to an undetectable level, demonstrating effective transplantation of protection from HIV infection.

This CIRM Disease Team Research Award proposes an approach to modify a patient's own HSC to circumvent the need to find matched donors that carry the delta-32 CCR5 mutation and while providing a renewable and long-lasting source of HIV-resistant cells. Specifically, the grant funds the development of a ZFN approach to treat AIDS patients by first isolating their HSC, modifying them using CCR5-specific ZFNs, and then re-infusing them to reconstitute the immune system with CCR5-negative, HIV-resistant immune cells.

"We are delighted that this research proposal was chosen for funding by CIRM," commented Dr. Philip Gregory, Sangamo's chief scientific officer and vice president, research. "This grant brings together a team of world-renowned experts to develop this novel ZFN-based stem cell therapy for AIDS-related lymphoma through to the clinic. We look forward to working with the team which includes Paula Cannon, Ph.D., associate professor of Molecular Microbiology & Immunology, Keck School of Medicine of the University of Southern California, who has carried out extensive pre-clinical research using our technology in stem cells, and Dr. Zaia and his colleagues at City of Hope who are pioneers in hematopoietic cell transplantation."

"CIRM support for this program is a major validation of our ZFP Therapeutics platform both scientifically and financially and we are very pleased to be part of the exceptional team that received the highest score of all of the grants reviewed by CIRM," said Edward Lanphier, Sangamo's president and CEO.

The CIRM Disease Team Research Awards will fund actively managed multidisciplinary teams engaged in milestone-driven translational research for the development of stem cell-based therapies. The mission of these teams will be to conduct the necessary research and regulatory activities to prepare and file a complete, well supported Investigational New Drug Application (IND) with the Food and Drug Administration (FDA) (and, if desired, other regulatory agencies), to enable Phase I clinical testing.



LINK:

http://investor.sangamo.com/releasedetail.cfm?ReleaseID=419462
« Last Edit: October 28, 2009, 08:17:32 PM by Inchlingblue »

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #28 on: October 28, 2009, 08:14:46 PM »
In addition to the grant for Sangamo, there will be $20 million for the AIDS Institute of the University of California, Los Angeles, which is partnering with Calimmune Inc. and using a different approach (RNAi) to silence CCR5.


Sangamo Gets Stem-Cell Grant for New AIDS Therapy
 
By Rob Waters

Oct. 28 (Bloomberg) -- Sangamo Biosciences, a developer of gene therapies based in Richmond, California, and the City of Hope, a nonprofit treatment center in Los Angeles, were awarded a $14.6 million grant to develop a new type of AIDS treatment.

California’s stem cell agency also will give $20 million to the AIDS Institute of the University of California, Los Angeles, which is partnering with Calimmune Inc., a closely held company based in Tucson, Arizona, to develop a related approach to AIDS treatment.

The grants are among a package of awards totaling more than $200 million approved today by the California Institute for Regenerative Medicine. The aim of the money is to help prepare treatments for human testing of stem-cell therapies within four years.

“It’s very exciting, a completely new paradigm for treating AIDS,” Jeff Sheehy, an HIV patient representative on the agency’s board, said about the City of Hope-Sangamo project in a telephone interview yesterday. “If it works, it could take AIDS treatment in a whole new direction.”

Sangamo fell 27 cents, or 4.4 percent, to $5.88 in composite trading on the Nasdaq Stock Market.

The two projects will use different methods to deactivate a gene called CCR5 that allows the AIDS virus to enter cells and spread infection, a new treatment approach. Both attempt to confer immunity to AIDS by mimicking the successful treatment of an AIDS patient in Germany.

Resisting Disease

That patient was able to stop drugs he had taken for 10 years, and remain healthy, after getting a transplant of stem cells from a donor with a rare gene variant known to resist the disease. The transplant also cured his leukemia, according to a report that appeared in February in the New England Journal of Medicine.

The unidentified 40-year-old patient had leukemia as well as HIV, the virus that causes AIDS, and needed a stem cell transplant to treat his cancer. The stem-cell donor was chosen because he is among the 1 percent of Caucasians who lack CCR5. Without the gene variant, the AIDS virus can’t enter a cell.

By giving the donor’s stem cells to the patient, doctors also gave him a new immune system that lacked CCR5. The experiment worked and the man is considered cured.

Kill the Cancer

The aim of the City of Hope-Sangamo effort is to treat patients with HIV and lymphoma, a blood cancer, killing the cancer by wiping out the patient’s immune system with chemotherapy. They will then use a genetic technology developed by Sangamo to modify the patients’ stem cells, which will be used to rebuild their immune system so they lack the CCR5 receptor.

“Cells that grow up following this process no longer have a functional copy of the CCR5 gene and no longer make the CCR5 protein,” said Philip Gregory, Sangamo’s chief scientific officer, in a telephone interview today. “If you don’t make it, then HIV can’t enter the cell. It’s a complete block to entry.”

The UCLA project will use a different method, attempting to turn off, or “silence,” the CCR5 gene using a technique known as RNA interference.


LINK:

http://www.bloomberg.com/apps/news?pid=20601124&sid=aP43cD4sNa8U

This is how these two projects were described in the New York Times:

Two projects will essentially try to replicate the reported cure last year of a patient with AIDS. The patient, in Berlin, also had leukemia and got a bone marrow transplant to treat that disease. But the bone marrow donor had a genetic makeup making him naturally resistant to H.I.V.

For a given patient with AIDS it would be nearly impossible to find a donor that is both a good match and naturally resistant to H.I.V. infection. But the two research teams plan to take a patient’s blood-forming stem cells and inactivate a gene to make them resistant to H.I.V., then put them back in the body.


LINK:

http://www.nytimes.com/2009/10/29/health/research/29stem.html
« Last Edit: October 29, 2009, 01:44:11 AM by Inchlingblue »

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #29 on: December 29, 2009, 10:30:47 PM »
The New York Times has an article on ZFN and Sangamo:

In New Way to Edit DNA, Hope for Treating Disease

LINK:

http://www.nytimes.com/2009/12/29/health/research/29zinc.html?pagewanted=1&_r=1&ref=science

Offline John2038

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #30 on: January 19, 2010, 01:22:47 PM »
Sangamo BioSciences Announces Presentation of Preliminary Data From Phase 1 Safety Trial of SB-728-T for HIV/AIDS
First Human Data from ZFN Clinical Program --ZFN-Modified Cells Well Tolerated and Able to Expand

RICHMOND, Calif., Jan 19, 2010

As expected, the subject's viral load increased during the STI. However, the kinetics of this subject's viral rebound was delayed. Presence of ZFN-modified cells in the GALT, an important HIV reservoir, demonstrates that we are achieving our pharmacologic biodistribution target. GALT HIV persistence in CD4+ T-cells is the reason that HIV is not eradicated in patients who are fully suppressed on highly active anti-retroviral treatment, or HAART. Ultimately, having a protected CD4+ T-cell population in the GALT may be extremely important in combating this disease.

"Our ZFN-based technology provides a totally new approach to HIV/AIDS with the aim of providing a reservoir of functional T-cells that are resistant to infection by HIV and available to fight opportunistic infections, and these data are an early indication that this may be possible."


Full Text

Offline John2038

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #31 on: January 20, 2010, 02:22:06 AM »
Just wanted to add a note:

1. The viral load increase during the STI was expected.
2. The viral rebound was delayed.
3. ZFN-modified T-cells were found also in the GALT, reaching the pharmacologic biodistribution target
4. ZFN-modified T-cells were well tolerated by the body and persisted in the circulation at stable levels for the duration of our monitoring.
5. In fact, more ZFN-modified T-cells were present at 20 weeks than were initially infused. Total CD4+ T-cell counts were also stable during this time.

These are important if not major achievements.

For those whose who haven't follows this research, here is how it work:

CD4+ T-cells are removed from the subject's blood and treated with Sangamo's ZFNs designed to modify the DNA sequence encoding the CCR5 gene.
This modification can occur directly in T-cells with only a brief exposure to the ZFNs. Once the CCR5 gene is modified, the gene is permanently disrupted in these cells.

The ZFN-modified T-cells are then infused into de patient.
These infused T-cell coexists with the original T-cells from the donor. So the expecred viral rebound but delayed.

As the infused T-cells can't be easily infected by HIV, they should at least remain present in the blood long enough for this approach to be interesting. And the results have shows so far (but in one patient) that not only it is the case, but that they persisted in the circulation at stable levels and even more, at 20 weeks (5 months) after the infusion.
In more the CD4 count have remain stable, which is what was also important.
The viral rebound was due to the infection of the original T-cell of this patient.

As such, we can dream that we can maintain with this appraoch a good level of healthy CD4, despite for eg viral failure. We can also hopes to boost the immune system of people undetectable.
Ultimately, we can hopes to better fight the residual viremia despite being UD, especially with a CD8 boost coming from another technology. As long as the CD4 level is in the normal range, despite a viral load detectable, the risk of developing OI/non-OI might be lowered (just a hope with no proof).
Finally, there are virtually no limits in the number of time the T-cell we can infused (excepting an economical limit), so such T-cell can help in the maintenance (and why not, the recovery) of exhausted immune systems.

All these are personal assumption, and only time will say. Lets hopes this can extends the life expectancy, delay the time to start HAART, allows STI, etc.. Dreaming a bit is not forbidden.

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #32 on: February 23, 2010, 05:53:47 PM »
Sangamo is starting a ZFN clinical trial in San Francisco.

LINK:

http://clinicaltrials.gov/ct2/show/NCT01044654?term=Sangamo&rank=1

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #33 on: February 25, 2010, 09:47:04 AM »
Another step in the right direction for the medicine of the (near?) future: Gene Therapy.
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Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #34 on: March 03, 2010, 09:26:49 PM »
RICHMOND, Calif., March 3, 2010 /PRNewswire via COMTEX/ -- Sangamo BioSciences, Inc. (SGMO 5.59, -0.07, -1.27%)  announced today that Edward Lanphier, Sangamo's president and CEO, will provide an update on the progress of Sangamo's ZFP Therapeutic(TM) development programs and an overview of the company's business strategy at 11:00 am ET on Wednesday, March 10, 2010 at the Cowen and Company 30th Annual Health Care Conference which will be held in Boston.

A live webcast of the presentation will be available on the Sangamo BioSciences website in the Investor Relations section http://investor.sangamo.com/index.cfm under Events and Presentations. A replay of the presentation will be archived on the Sangamo website for two weeks after the event.


LINK:

http://www.marketwatch.com/story/sangamo-biosciences-announces-presentation-at-cowen-and-company-health-care-conference-2010-03-03?reflink=MW_news_stmp

Offline Pepino2

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #35 on: March 10, 2010, 03:25:57 PM »
Cowen and Company 30th Annual Health Care Conference
Speaker: Edward Lanphier, President and CEO

Sangamo BioSciences
 (SGMO: NASDAQ)

SB-728-T Data Presentation: Due end of 2010
 Current Stock price: $5.92
52 week high: $8.75

Forecast:  Bullish :)

Offline Cosmicdancer

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #36 on: May 13, 2010, 01:18:06 AM »
Here's an audio presentation by Sangamo at the Bank of America Merrill Lynch Health Care Conference
on Wednesday in NYC. 

The presenter talks about several of their zinc finger therapeutics, and discusses their Phase 1 HIV trials at U Penn and in San Francisco at about the 19:50 minute mark.  He said they expect to have results by the end of this year or early next year. 

https://www.veracast.com/webcasts/bas/healthcare2010/id78403470.cfm
Summer, 2007 - &$#@?
November, 2007 - Tested poz, 300,000 vl, 560 cd4
Feb, 2008 - 57,000 vl, 520 cd4, started Atripla
June, 2008 - undetectable, 612 cd4
January, 2009 - undetectable, 670 cd4
May, 2009 - undetectable, 593 cd4
Sept, 2009 - 83 vl, 763 cd4, 34%
Dec, 2009 - undetectable, 889 cd4, 32%
April, 2010 - undetectable, 860 cd4, 31%
October, 2010 - undetectable, 800 cd4, 38%
April, 2011 - undetectable, t-cell test not done
October, 2011 - undetectable
April, 2012 - undetectable, 850 cd4, 39%
November, 2012 - undetectable, 901 cd4, 41%
April, 2013 - undetectable, 846 cd4, 36%
October, 2013 - undetectable
May, 2014 - undetectable, 784 cd4, 48%

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #37 on: July 12, 2010, 01:55:18 PM »
Sangamo BioSciences Publishes Data Indicating the Use of Zinc Finger Nucleases to Generate HIV Resistant Human Stem Cells

Posted on: Mon, 12 Jul 2010 00:40:56 EDT

Sangamo BioSciences, Inc. has announced the publication of data demonstrating the preclinical efficacy of a human stem cell therapy for human immunodeficiency virus (HIV) based on its proprietary zinc finger DNA-binding protein nuclease (ZFN) technology.

In a release, the Company noted:

The ZFN approach enables the permanent disruption of the CCR5 gene, which encodes an important receptor for HIV infection, in all the cell types comprising the immune system that develop from hematopoietic stem cells (HSCs), and is the basis for a promising therapeutic strategy for the treatment of HIV/AIDS. Sangamo has two ongoing Phase 1 clinical trials to evaluate the safety and clinical efficacy of this approach in CD4+ T-cells.

The work, which was carried out in the laboratory of Paula Cannon, Ph.D., Associate Professor of Molecular Microbiology & Immunology at the Keck School of Medicine of the University of Southern California (USC), in collaboration with Sangamo scientists, was published on July 2, as an Advance Online Publication (nature.com/nbt/journal/vaop/ncurrent/full/nbt.1663.html) in Nature Biotechnology.

"These are very exciting data that provide proof of concept for a new approach to HIV treatment," said John Zaia, M.D., the Aaron D. and Edith Miller Chair in Gene Therapy and Chair of Virology, City of Hope. "The recent example of the 'Berlin Patient' who appears to have been cured of both his HIV and leukemia by receiving a bone marrow transplant (BMT) of stem cells from a donor that had a naturally occurring CCR5 mutation that makes them resistant to HIV infection, provided the model for this approach. However, the paucity of human donors with this natural CCR5 mutation and the risks of allogeneic BMT mean that we need a more practical solution to make this a therapeutic option. Modification of HSCs using ZFNs to recreate the CCR5 mutation is a potential solution."

"The data described in this paper are an important demonstration of the potential therapeutic possibilities of ZFN modification of human stem cells," said Philip Gregory, D. Phil., Sangamo's vice president of research and chief scientific officer. "We have demonstrated efficient and specific modification of human hematopoietic stem cells, rendering them resistant to infection with HIV-1 while retaining their 'stemness' and ability to differentiate. These data pave the way for the use of this technology in other diseases for which HSC modification may be therapeutically useful."


LINK:

http://www.tradingmarkets.com/news/stock-alert/sgmo_sangamo-biosciences-publishes-data-indicating-the-use-of-zinc-finger-nucleases-to-generate-hiv-resis-1033590.html

Offline veritas

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #38 on: July 13, 2010, 05:46:22 AM »

inch,

ZFNs seem to be very credible. More research is being done in China (sort of like peer review) whereby ZFNs are being used to fight hiv with respect to integrase and transcriptase. Thus more than one way to go after hiv. However, blocking ccr5 seems to be the way to go (prevent hiv  from establishing in the first place).

I like what Sangamo is doing with respect to neuropathy also. Applications for this therapy  are endless. I wonder if it could help with lipo?

Exciting stuff.

v

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #39 on: July 13, 2010, 10:35:21 AM »
I Zinc Fingers too.

Can you feel the love? 
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Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #40 on: July 13, 2010, 11:00:41 AM »
inch,

ZFNs seem to be very credible. More research is being done in China (sort of like peer review) whereby ZFNs are being used to fight hiv with respect to integrase and transcriptase.

v

I googled "China HIV zinc finger" and could not find anything; if by any chance you have any more info I'd love to read it.

Thanks ;)

Offline veritas

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #41 on: July 13, 2010, 04:40:06 PM »

Inch,

Here's a peer review with respect to ZFNs:

http://www.biomedcentral.com/content/pdf/1741-7015-8-42.pdf

Seems you can manipulate almost any gene you desire. The above link is a better review. Let me know what you think.

v

Offline freaky_dream

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #42 on: August 21, 2010, 10:35:34 PM »
New article in the LA times about a potential gene therapy being developed in conjunction with City of Hope. It involves Zinc Finger of course and injecting into the bone marrow hoping to illicit the same results as the German transplant patient who was cured of HIV. They are aiming to receive FDA approval to start trials in 3-4 years. The research was funded by a California voting initiative for Stem Cell Research (yup sometimes Californians do vote for the right things...)


http://www.latimes.com/news/science/la-sci-hiv-therapy-20100822,0,2873266.story?page=1&track=rss
« Last Edit: August 21, 2010, 10:38:30 PM by freaky_dream »

Offline MitchMiller

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #43 on: August 21, 2010, 10:50:56 PM »
$100k for the treatment sounds outrageous.  By the time it's approved, many of the existing ARVs will be off patent and SHOULD be MUCH cheaper.  (I shout out those words because the US drug distribution system seems to be completely disfunctional, so it's anyone's guess if logic will prevail in a rigged marketplace.)

So this sounds like an interesting academic exercise, but I question whether it would ever have practical application given the costs.... even if it is a cure.

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #44 on: August 22, 2010, 02:27:31 PM »
$100k for the treatment sounds outrageous.  By the time it's approved, many of the existing ARVs will be off patent and SHOULD be MUCH cheaper.  (I shout out those words because the US drug distribution system seems to be completely disfunctional, so it's anyone's guess if logic will prevail in a rigged marketplace.)

So this sounds like an interesting academic exercise, but I question whether it would ever have practical application given the costs.... even if it is a cure.

Somehow it's hard to imagine that if this does prove to work and is a cure, functional or otherwise, it would remain an "interesting academic exercise".  How or if it's subsidized and even if the purported cost of 100k is accurate, there's no way that a proven cure will simply languish out there because it's "too expensive".  Can you imagine the hell that would be raised if news came out that a cure was discovered but too bad bastards you don't get it it costs too much?  Not going to happen.
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Offline xman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #45 on: August 22, 2010, 08:03:34 PM »
No it will not happen but, as anything in this wonderful world, those in Third World Countries would be the last to benefit from this scientific conquest giving the pharmaceutical companies any possibility to exploit their meds for the maximum. I hope that a cure, even functional, would be affordable for the mass and given for free for those who can't afford it.
sign the petition launched by the aids policy project addressed to the nih aimed to increase the money needed to find the cure:

http://www.aidspolicyproject.org/petition_for_the_nih

we can make a difference and we need to fight. please support them! it doesn't cost you anything. they need it now more than ever!

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #46 on: September 14, 2010, 01:14:35 PM »
HIV/AIDS activist Matt Sharp is taking part in the Sangamo ZFN trial:

http://aidspolicyproject.blogspot.com/2010/09/aids-activist-participates-in-clinical.html

Offline ElZorro

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #47 on: September 14, 2010, 06:07:41 PM »
Excellent post....let's hope the trial is successful for Matt who surely deserves to benefit after all he has been through as well as for the rest of us

Offline sam66

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #48 on: September 14, 2010, 11:22:58 PM »

  Good luck and all the best Matt,  my thoughts are with you

   sam
december 2007 diagnosed +ve ,

Offline Inchlingblue

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #49 on: December 07, 2010, 09:36:39 AM »
Sangamo recently presented very good results for some of their other ZFN trials (not the HIV ones). It might be a good sign overall for this approach actually working. Time will tell.

As far as HIV, Sangamo's bio mentions that they have:

a Phase 1 / 2 clinical trial and two ongoing Phase 1 clinical trials to evaluate the safety and efficacy for the treatment of HIV/AIDS

Sangamo BioSciences Announces Data Presentation of First In Vivo Demonstration of ZFN-mediated Gene Correction Via Systemic Delivery at American Society for Hematology Meeting

LINK:

http://www.prnewswire.com/news-releases/sangamo-biosciences-announces-data-presentation-of-first-in-vivo-demonstration-of-zfn-mediated-gene-correction-via-systemic-delivery-at-american-society-for-hematology-meeting-111435574.html

 


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