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Author Topic: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach  (Read 161132 times)

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Offline Dr.Strangelove

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #300 on: July 12, 2012, 05:25:50 PM »
The 1% or so of the population that has a mutation of both their CCR5 genes seems to be doing fine without the CCR5 receptor being functional.

Offline misterprice

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #301 on: July 12, 2012, 05:41:03 PM »
The 1% or so of the population that has a mutation of both their CCR5 genes seems to be doing fine without the CCR5 receptor being functional.

Yeah, they seem to be doing fine. Have a good read.

Eri, R, et al., CCR5-Delta 32 mutation is strongly associated with primary sclerosing cholangitis. Genes And Immunity 5(6):444–450, September 2004.

http://www.nature.com/gene/journal/v5/n6/full/6364113a.html

Ad I said, the CCR5 receptor plays an important role in the inflammatory process.
« Last Edit: July 12, 2012, 06:37:38 PM by misterprice »

Offline Skydrake

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #302 on: July 13, 2012, 05:37:13 AM »

And what about astrocytes in the brain?
The zinc theraphy aims to change the  CCR5 receptor only in lymphocytes T.
The replication in the brain will continue, even faster without antiretroviral.

http://explore.georgetown.edu/news/?ID=64534&PageTemplateID=295
http://www.hiv-reservoir.net/index.php/the-news/85-bioinformatics-and-hiv-in-the-brain.html

Most ART drugs have a certain penetration in the brain:


No ART, even with no CCR5 lymphocytes, means to maximize the replication in the brain by astrocytes.
Is the target of zinc therapy to make survive hiv+ but with HIV-related dementia?

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #303 on: July 13, 2012, 10:08:58 AM »
Is the target of zinc therapy to make survive hiv+ but with HIV-related dementia?

Yes, it's all a big conspiracy.  Sangamo's evil plan is to create an army of HIV dementia zombies that they can control to take over the world.

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Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #304 on: July 13, 2012, 10:19:04 AM »
Yeah, they seem to be doing fine. Have a good read.

Then again, there's opinions like this:

"It’s highly unusual,’ says Dr. Stephen J. O’Brien of the National Institutes of Health in Washington D.C. ‘Most genes, if you knock them out, cause serious diseases like cystic fibrosis or sickle cell anemia or diabetes. But CCR5-delta32 is rather innocuous to its carriers. The reason seems to be that the normal function of CCR5 is redundant in our genes; that several other genes can perform the same function".
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Offline misterprice

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #305 on: July 13, 2012, 01:06:54 PM »
Yes, it's all a big conspiracy.  Sangamo's evil plan is to create an army of HIV dementia zombies that they can control to take over the world.

Well, besides his obvious evil plan, what we are saying is that there are much, much better approaches than the Sangamo's one. At this point, you better stick to Maraviroc, at least if you experience side effects, you can just stop the therapy. However, there is no coming back from gene therapy.
« Last Edit: July 13, 2012, 01:22:21 PM by misterprice »

Offline misterprice

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #306 on: July 13, 2012, 01:10:00 PM »
Then again, there's opinions like this:

"It’s highly unusual,’ says Dr. Stephen J. O’Brien of the National Institutes of Health in Washington D.C. ‘Most genes, if you knock them out, cause serious diseases like cystic fibrosis or sickle cell anemia or diabetes. But CCR5-delta32 is rather innocuous to its carriers. The reason seems to be that the normal function of CCR5 is redundant in our genes; that several other genes can perform the same function".

Yes, opinions.

"There are in fact two things, science and opinion; the former begets knowledge, the latter ignorance." Hippocrates

We better stick to facts; therefore, we better stick to the data reported in scientific literature.

« Last Edit: July 15, 2012, 12:37:34 PM by misterprice »

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #307 on: July 13, 2012, 02:02:46 PM »
ignorance

Best do some better research there, slim.  The study you cite from 2004 has been repudiated. 

You can stick to Maraviroc and pardon me if I take the word of an NIH doc over yours.  That is, unless you'd like to share your credentials with the board  :)

EDIT: 

Hmmm....here's an interesting piece of scientific literature:

http://www.ncbi.nlm.nih.gov/pubmed/16633049

"Because an intact CCR5 receptor is needed for internalization of specific pathogens and homing of memory T lymphocytes to the liver, we hypothesize that a deficient expression of this receptor resulting from the CCR5-Delta32 variant may protect against PSC."

Clown


« Last Edit: July 13, 2012, 02:49:57 PM by freewillie99 »
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Offline Ann

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #308 on: July 13, 2012, 03:31:32 PM »

Clown


Willy, I hope you were signing your post Clown rather than calling misterprice a clown. Surely you know that name-calling isn't permitted here. Right?
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Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #309 on: July 13, 2012, 03:57:08 PM »
Willy, I hope you were signing your post Clown rather than calling misterprice a clown. Surely you know that name-calling isn't permitted here. Right?

Absolutely it was a sign-off, Ann.  After recently watching The Dark Knight again and taking inspiration from Heath Ledger's Joker, it was kind of a trial balloon, a stab at re-branding, if you will.  Never would I accuse a troll fellow poster like misterprince of being a clown.  He's obviously a fine source of expertise.
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Offline misterprice

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #310 on: July 13, 2012, 04:34:41 PM »
Best do some better research there, slim.  The study you cite from 2004 has been repudiated. 

Can you please provide a reliable source for this ?

Quote
You can stick to Maraviroc and pardon me if I take the word of an NIH doc over yours.That is, unless you'd like to share your credentials with the board  :)


Yes, I will stick to Maraviroc. If one day this gene therapy will be FDA approved, then I will change my mind about it. Opinions are just opinions. You should never take the opinion of someone as a fact, just because he has credentials.

Quote
EDIT: 

Hmmm....here's an interesting piece of scientific literature:

http://www.ncbi.nlm.nih.gov/pubmed/16633049

"Because an intact CCR5 receptor is needed for internalization of specific pathogens and homing of memory T lymphocytes to the liver, we hypothesize that a deficient expression of this receptor resulting from the CCR5-Delta32 variant may protect against PSC."

In this paper someone hypothesizes that a deficient expression of this receptor resulting from the CCR5-Delta32 variant may protect against PSC. This is called speculation. Yes, speculation is present in scientific literature. If you say you "hypothesize", then you are speculating, it means the data of your study do not provide enough evidence of something. However, in the study that I cited, they claim there is evidence.

"This study provides evidence for an association between PSC and the chemokine receptor family, with a significantly increased frequency of CCR5-Delta32 heterozygotes (P=0.003) and a significantly higher CCR5-Delta32 allele frequency (P=0.007) in PSC patients compared to matched controls. CCR5-Delta32 was also significantly commoner in PSC compared to a large, unselected series of patients with IBD alone (P=0.027).

http://www.nature.com/gene/journal/v5/n6/full/6364113a.html

The tone is totally different.

Quote
Clown

Yep, we all love Batman the Dark Knight  ;)





« Last Edit: July 13, 2012, 07:57:06 PM by misterprice »

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #311 on: July 13, 2012, 06:31:27 PM »
Yep, we all love Batman the Dark Knight  ;)

Speaking of the Dark Knight (and clowns)...love this:

http://www.youtube.com/watch?feature=player_embedded&v=bdb2w1Yu97E
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Offline misterprice

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #312 on: July 13, 2012, 07:50:33 PM »

Offline Mishma

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #313 on: July 14, 2012, 01:59:22 PM »
A common misconception made in treating any infectious disease is that a drug/treatment has to kill off ALL of the pathogens in order to be effective. The reality is that one need only tip the balance in the host's favor. Host factors/cells can then eliminate or control the infection.

Even Mr. Brown has evidence of HIV provirus in his body-thus proving the point. He doesn't have active HIV and is at this point functionally cured.

2016 CD4 25% UD (less than 20). 27+ years positive. Isentress, Truvada, Acyclovir, Clonazepam, Zolpidem, Bupropion, Lisinopril, Pravastatin, Quetiapine, Doxcycline, Testosterone, Suatriptan/Naproxen, Restasis, Dorzolamide, Latanoprost, Asprin, lortab, Levothyroxine, Fioricet, Restasis, Triamclinolone, Nitrostat.

Offline Skydrake

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #314 on: July 15, 2012, 06:49:46 AM »
Best do some better research there, slim.  The study you cite from 2004 has been repudiated. 

You can stick to Maraviroc and pardon me if I take the word of an NIH doc over yours.  That is, unless you'd like to share your credentials with the board  :)

???
About Maraviroc, there is a interesting study one month old

http://forums.poz.com/index.php?topic=43938.0

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #315 on: July 19, 2012, 08:05:09 AM »
http://www.npr.org/blogs/health/2012/07/18/156988650/hiv-cure-is-closer-as-patients-full-recovery-inspires-new-research?ps=sh_stcathdl

Thought this was interesting.  Most of the article linked to above is more of the same old stuff, however, about halfway through there's this:

Gregg Cassin is a human guinea pig in an experiment sponsored by Sangamo Biosciences, a California-based company. His experience provides a tantalizing clue that gene therapy against HIV might work.

Cassin thinks he got HIV in the early 1980s. He didn't start antiviral treatment until his immune cell counts plunged to near-zero. He's watched many friends get sick and die from AIDS while he's remained healthy.

Last year Cassin volunteered for the gene therapy experiment. "I wanted to get into the next exciting thing in research," he says, "and completely by accident, I found out I had one of these mutations, the CCR5 mutation."

That's the same mutation that Brown's bone marrow donor had — the genetic quirk that makes him immune to HIV. But Cassin has only one out of two possible mutations, while the Berlin patient's donor has both. So Cassin is only partly protected. But it may explain why he has survived so many years of HIV infection without treatment.

In the gene therapy trial, researchers took out some of Cassin's immune cells and treated them with a chemical called a zinc-finger protease that knocks out both CCR5 genes. Then they grew billions of these engineered cells and injected them back into Cassin.

After a few weeks, according to plan, Cassin stopped taking anti-HIV drugs. He was off therapy for several weeks. But then he panicked.

"This is the part I feel a little bit bad about, a little embarrassed about," Cassin says. "But my viral load shot up, and I got nervous. So I went back onto treatment."


He may have panicked too soon. Two weeks later, Cassin got the results of his latest blood test, which had been done just before he resumed treatment. It showed the amount of HIV in his blood had started to drop sharply, even without antiviral drugs in his system.

"My body was taking care of it," he says.


Scientists will never know whether his viral load, as it's called, would have continued to drop, as Brown's did after a similar initial spike. That will take many more patients who have more definite and lasting benefits.


This guy is a heterozygote, like the so-called "Trenton patient", who went undetectable (after an initial vl spike as well).  Not exactly sure what to make of this.  Sangamo will be coming out with trial related info at the end of August I believe.  Stay tuned.
« Last Edit: July 19, 2012, 08:07:41 AM by freewillie99 »
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Offline Mishma

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #316 on: July 20, 2012, 06:48:41 PM »
Risks abound in human trials. Promising first results and legitimate concerns but we still have phase 3 and 4 trials to come. We need the numbers to prove (or disprove) the hypothesis and prove efficacy and safety.
 
2016 CD4 25% UD (less than 20). 27+ years positive. Isentress, Truvada, Acyclovir, Clonazepam, Zolpidem, Bupropion, Lisinopril, Pravastatin, Quetiapine, Doxcycline, Testosterone, Suatriptan/Naproxen, Restasis, Dorzolamide, Latanoprost, Asprin, lortab, Levothyroxine, Fioricet, Restasis, Triamclinolone, Nitrostat.

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #317 on: July 26, 2012, 12:05:23 AM »
They announce today that the results of the current trials won't be released until next year.  WTF?  They know how well it's working -- they've got patients using it, off their meds, etc.  They know by now if their VLs are coming down.  Just let us know what's happening already.

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #318 on: August 02, 2012, 12:56:32 PM »
This was an interesting interview -- from student at Barbas' lab at the Scripps institute re: naked delivery of ZFNs.  Sure seems promising --

http://backstory.scienceblog.com/2012/07/20/a-gene-free-gene-therapy/

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #319 on: September 10, 2012, 08:13:12 PM »
We've got a couple of Sangamo threads out there -- responding back on this one since it seems to have the most content.

As reported on a different thread, Sangamo released more data from their Phase I study.  They got some good press from it, the stock price went up but... and a big but... there really isn't that much new news here.  They talk about "immune reconstitution" -- meaning that your T-Cells return to a normal level.  That's fantastic.  It means that the treated HIV-resistant cells hang around and multiply.  This, though, was already known.

What is NOT known is the effect on viral load.  We won't know about this until the first half of next year when preliminary results are released from the Phase II (hetero and cytoxan/increase uptake) trials.  The best part about the news today is that, so far, things seem to be working as they expected.  Also, Sangamo has long speculated that it'll take 10-15% of your T-Cells to be immune before VL will come down.  They are gathering a lot of evidence / data to back up that claim. 

While agonizingly slow progress is being made, it *is* being made and I'm hoping for good news in 2013. 

Offline Dr.Strangelove

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #320 on: September 10, 2012, 09:48:30 PM »
Thanks for the update.
I am always a little skeptic when it comes to research updates from pharma companies. They have a lot of pressure from investors to deliver, so whatever they say should be taken with a grain of salt.

I am also quite curious to see the effects of their therapy in VL.

You'v mentioned the thing with "15% immune T-cells = major reduction of VL" before. I find it quite counter intuitive and would love to understand what is Sangamo's reasoning behind this theory. Perhaps I just missed something. Do you happen to have a link where they talk about this? Thanks.

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #321 on: September 11, 2012, 01:05:46 AM »
I'm trying to remember where I heard it -- I say "heard" it b/c I think it was during a live session either on a conference call or a video of one of the conferences.   I'll hunt around for it.

This slide show is a recap of where they are / what information has been released right now:

http://www.slideshare.net/RHMBONCO/sangamos-hiv-study-slides-dr-1-morales-borges-of-arc-091212

What I didn't get the significance of until just now was Slide 14, "Asymptomatic Rectal Inflammation".  It looks like the modified cells homed in on the rectal tissue and normalized it.   I was talking to my Dr. the other day and asked why, if I'm on meds, I still have high CD8s.  She explained that though I had no HIV in my plasma, I still had it in my tissues and this was causing inflammation.  Then I saw this slide and I realized what she was talking about.  SB728-T is reducing (eliminating?) inflammation (and presumably HIV) in the tissues.  That seems like a very significant finding to me.

I'm a computer programmer -- not a Dr.  Just trying to put the pieces together as best I can.  -- George

Offline Dr.Strangelove

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #322 on: September 11, 2012, 02:01:16 AM »
Thanks for the link.

Hmm, don't know about the "Asymptomatic Rectal Inflammation".

I'm a biologist but my field is not directly related to HIV or immunology.

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #323 on: September 11, 2012, 02:23:44 AM »
Ah, I found a mention of the 10-15% figure.

Here's a link to the Sangamo website --

http://investor.sangamo.com/events.cfm

Click the second link on the page -- a conference call entitled "2012 PacGrow Lifesciences Management Access Conference". 

At about 10 minutes into the talk, Ed Lanphier talks about the 10-15% therapeutic window that, he says, should drive a patient to be undetectable.


Offline Dr.Strangelove

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #324 on: September 11, 2012, 11:04:07 PM »
Thanks. Let e know if you find more...

I'm looking forward to see their data on the effect of the viral load next year. And I wonder how often you will need to get a fresh ZFN-treated T-cell infusion to remain UD.

Offline NYCguy

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #325 on: October 09, 2012, 03:57:59 PM »
I've been following Sangamo for years.. VL allso seemed to me to be conspicuously missing from the latest results.  Why aren't they at least giving a little data?  Hopefully next year we will get something significant and they will start testing the next tweak.  Anyone know if that guy who was in the study is still posting somewhere?
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Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #326 on: October 09, 2012, 05:09:46 PM »
I think you're referring to Matt Sharp.  As I understand it, he was in the first Sangamo trial.  He did seem to get a significant and permanent increase in his T-Cells.  All of these first patients had viral loads decline and then went back on meds, one (the heterozygote) went UD. 

Here's Matt Sharp:

http://www.youtube.com/watch?v=arJSYJpBvI4

The only story I've seen regarding a patient in the new trials is about  Greg Cassin.  He did undergo the STI, and it looks like his body was bringing his VL down, but then he got a little nervous about being off meds and went back on HAART.  Here's the link:

http://www.npr.org/blogs/health/2012/07/18/156988650/hiv-cure-is-closer-as-patients-full-recovery-inspires-new-research

We should know by the first half of next year the results of the new trials and whether VL's are coming down or not.  My guess (no insider knowledge) is that they'll announce preliminary results at CROI in March.

Ed Lamphier of Sangamo continues to talk about achieving a functional cure for HIV -- that's a good sign.  (Of course, he also spoke very positively about their treatment for diabetic neuropathy shortly before the disappointing results were announced).  Also, if there was someone out there on one of the trials (either the hetero trial or the cytoxan trial) who had achieved undetectability, you'd think the word would have gotten out by now.  Their stock price bumps around a lot, and is about where it was last year -- this indicates to me that little or no information (good or bad) has leaked about the trials.
« Last Edit: October 09, 2012, 05:21:02 PM by geobee »

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #327 on: October 30, 2012, 11:45:42 PM »
Here's another CCR5 knockout strategy that seems to compete with Sangamo.  From the Hutchinson center in Seattle.  They argue it's more efficient.  Here's the link:

http://pulse.seattlechildrens.org/gene-repair-breakthrough-led-by-seattle-childrens-research-institute/

Offline Jmarksto

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #328 on: October 31, 2012, 01:39:19 AM »
Geobee;  Thanks for the post on the Seattle Childrens research -- I think this link warrants its own thread.

I generally take these announcements with a very large grain of salt.  However, the credibility of these organizations reduces the amount of salt required.  Also, there is some irony in their lack of funding and their geographical proximity to the Gates Foundation.  They are a short city bus ride away from significant funding for HIV research. 

Lets hope they can advance this technology!

JM

« Last Edit: October 31, 2012, 01:42:28 AM by Jmarksto »
03/15/12 Negative
06/15/12 Positive
07/11/12 CD4 790          VL 4,000
08/06/12 CD4 816/38%   VL 49,300
08/20/12 Started Complera
11/06/12 CD4   819/41% VL 38
02/11/13 CD4   935/41% VL UD
06/06/13 CD4   816/41% VL UD
10/28/13 CD4 1131/45%  VL 25
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Offline Ann

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #329 on: October 31, 2012, 03:32:13 AM »

I generally take these announcements with a very large grain of salt.  However, the credibility of these organizations reduces the amount of salt required.


Me too, but the way you put this made me think of those very large blocks of salt some people put out for deer. ;)
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"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline Jmarksto

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #330 on: October 31, 2012, 07:27:48 PM »
Me too, but the way you put this made me think of those very large blocks of salt some people put out for deer. ;)

Ahhh, a salt lick...which would be the appropriate size "grain" for the Koronis KP1461 technology.

JM
03/15/12 Negative
06/15/12 Positive
07/11/12 CD4 790          VL 4,000
08/06/12 CD4 816/38%   VL 49,300
08/20/12 Started Complera
11/06/12 CD4   819/41% VL 38
02/11/13 CD4   935/41% VL UD
06/06/13 CD4   816/41% VL UD
10/28/13 CD4 1131/45%  VL 25
02/25/14 CD4   792/37%  VL UD
07/09/14 CD4 1004/39%   VL UD
11/03/14 CD4   711/34%   VL UD

Offline Ann

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #331 on: November 01, 2012, 06:40:14 AM »
Ahhh, a salt lick...which would be the appropriate size "grain" for the Koronis KP1461 technology.

JM

'Zactly what I was thinking! You really do need a rather large grain of salt when reading many of these cure theories. Not to say we shouldn't hope for a cure some day, but we need to be realistic about it - and keep the salt handy.
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"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #332 on: November 06, 2012, 04:14:19 PM »
So I'm being re-screened for the Sangamo trial.  I was DQ'd before because of high bilirubin (I'm on Reyataz) but, after Dr. Jay sent out an email looking for more recruits, I contacted him and they decided to re-screen me.   They're testing my T-Cells, tropism and levels of adenovirus antibodies.

Apparently it's difficult to do a tropism test on people that are undetectable (as I gratefully am) because, of course, there isn't much virus to test.  It can take 6 weeks to 2 months for the test results to be ready. 

Second, tropism with respect to this trial is important -- if you go off meds and have X4 and R5 virus then of course your viral load will go up as the Sangamo modification in this trial only affects the R5 receptor on the T-Cell.

I'm waiting for the results, will keep you all posted when they come back.

Update:  Well, I hit the "save" button here on AM and then Quest called.  Turns out my A5 titer is high -- DQ'd again.  They said that this goes up and down and they'll test again in 6 months.
« Last Edit: November 06, 2012, 06:01:14 PM by geobee »

Offline Jmarksto

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #333 on: November 06, 2012, 07:38:03 PM »
geobee;  Thanks for the update and I wish you well with retesting!

JM
03/15/12 Negative
06/15/12 Positive
07/11/12 CD4 790          VL 4,000
08/06/12 CD4 816/38%   VL 49,300
08/20/12 Started Complera
11/06/12 CD4   819/41% VL 38
02/11/13 CD4   935/41% VL UD
06/06/13 CD4   816/41% VL UD
10/28/13 CD4 1131/45%  VL 25
02/25/14 CD4   792/37%  VL UD
07/09/14 CD4 1004/39%   VL UD
11/03/14 CD4   711/34%   VL UD

Offline Matts

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #334 on: November 08, 2012, 07:42:19 PM »
Good luck with this experiment:)

Maybe we all can benefit from that in 10 years.
Gero Hütter's "Berlin Patient" Timothy Brown is living without meds for 5 years, so there is a evidence that the "CCR5 thing" could work.
Let's see.
triumeq

Offline Markmt

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #335 on: November 13, 2012, 04:38:54 PM »
Thank you for keeping us informed Geobee!! Fingers crossed for good results :)
"Live to love and love to live."

Leo Buscaglia

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #336 on: January 02, 2013, 04:17:49 PM »
Just wanted to to post a quick note re: Sangamo. 

From reading various internet sources, I think Sangamo will have preliminary results from their two trials (the hetero trial and the cytoxan trial) at CROI 2013, which takes place March 3 through 6. 

Enrollments in both trials have gone reasonably well, so by March there should be patients who have completed both trials -- undergone the infusion and then had the structured treatment interruption.

There are so many gray areas in medicine, but this data, hopefully, will tell us if SB728 works and for whom it works.   (And by "works" I mean reduces viral loads to undetectable levels, a "functional" cure).

Sangamo's Plan B is to treat stem cells (instead of TCells).    CalImmune, which I've heard little about, also plans to modify stem cells.




Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #337 on: January 02, 2013, 06:19:07 PM »
Let's hope Sangamo's "Plan B" works better than Boehners...
Beware Romanians bearing strange gifts

Offline Markmt

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #338 on: January 11, 2013, 07:15:04 AM »
Sangamo BioSciences’ CEO Presents at 31st Annual J.P. Morgan Healthcare 9th January 2013.

(scroll down till you get to the above title. Than read Edward Lanphier presentation where he includes HIV of course ) Nothing new said, just that it stays upbeat :)

http://www.sctpn.net/1viralvoice/author/diradiocast/
"Live to love and love to live."

Leo Buscaglia

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #339 on: January 14, 2013, 04:58:02 PM »
Sangamo shares up 17% today.  Haven't seen any reason for the movement but something is going on. 

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #340 on: January 14, 2013, 06:54:13 PM »
Was going to post something about that as well.  Up 17% and over 4x average volume on no news?  HIV is their primary claim to fame?  CROI 2013 late breaker registration deadline on Weds? 

Conspiracy theories abound.
Beware Romanians bearing strange gifts

Offline xman

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #341 on: January 15, 2013, 03:25:56 PM »
Sangamo BioSciences: A Potentially Revolutionary 2013

By Ivan Deryugin

In medicine, there are certain watershed moments that become an enduring part of medical history, such as the discovery of penicillin, or the eradication of smallpox. Sangamo BioSciences (SGMO) has a chance of joining the ranks of such key medical milestones, as the company is working on one of the greatest unmet needs in medicine - a functional cure for HIV and AIDS. Sangamo is set to report new clinical data regarding its development-stage HIV/AIDS treatment this year, and if all goes well, the stock will soar as the market for an effective treatment remains wide open. The company is well capitalized to continue development of its pipeline, and considering the vast market potential of its lead candidate, shares offer a quality risk/reward, even following SGMO's impressive gains in the last year. Nevertheless, a binary biotechnology event requires risk tolerance, and we include two options strategies for the risk-averse investor.

Overview

Sangamo was founded in 1995, and since inception has spent over $270 million on the development of its ZFP technology. ZFP's, known technically as zinc finger binding proteins, are proteins that recognize and bind to a person's DNA. Sangamo uses these to create ZFP transcription factors that are able to turn genes on or off. When these proteins bind to DNA, they can regulate the expression of any gene in any type of cell. In addition, Sangamo has created ZFP nucleases (also known as ZFN's) that can be used in therapeutic gene modification. Sangamo's goal is to disrupt the mechanism of HIV/AIDS (as well as other diseases), and hopefully, find a way to emerge victorious in what many see as medicine's last frontier.

Since going public in 2000, Sangamo has lost over 45% of its value, as setbacks have called into question the company's positioning and strategy. But, shares have risen around 150% in the past year, as Sangamo has renewed hopes that it can triumph in the fight against HIV/AIDS. And if all goes well in 2013, gains should continue.

SB-728-T: A New Approach to HIV/AIDs

Sangamo's lead product is SB-728-T, a ZFN-based therapy whose goal is to be a functional cure for HIV/AIDS, and not just a treatment. Before I delve into the clinical data (and the path forward) for SB-728,  a review of HIV/AIDS is in order, as SB-728 has a truly unique mechanism of action. When a person is infected with HIV, the virus destroys their immune cells, specifically their CD4+ T-cells. The HIV virus binds to the surface of CD4+ cells using the viral envelope protein gp120. Once this happens, the HIV virus fuses into its host cell via a fusion peptide, thereby allowing their cellular membranes to fuse. The HIV virus leads to a steady reduction in a patient's CD4+ T-Cells, with 200 cells per microliter being the delineating line between HIV and AIDS (500-1200 in healthy adults). SB-728 targets HIV by targeting CCR5, a co-receptor that HIV uses to enter a person's T-cells. But, if CCR5 is absent from the surface of these T-cells, the HIV virus becomes less efficient. This is where SB-728-T comes in.

It has been discovered that a small subset of the HIV patient population has a natural mutation, known as CCR5Δ32, which renders patients essentially immune to HIV (it is thought that this mutation arose during the Black Death; research has shown that the bubonic plague does not "associate" with the mutation). Studies have shown that patients who have just one allele with the CCR5Δ32 mutation saw a 2-year delay in the onset of AIDS. Sangamo's goal with SB-728 is to replicate this mutation to disrupt the CCR5 gene of HIV patients to make their immune system permanently resistant to HIV. In late 2010, doctors performed a bone marrow transplant on a patient who had both leukemia and AIDS, and saw that the patient no longer had any detectable viral loads, and no longer needed anti-retrovirals. The donor from whom the bone marrow was donated had the CCR5Δ32 mutation, and it "transferred over" to the leukemia/AIDS patient. With SB-728-T, Sangamo hopes to repeat this kind of clinical result in all HIV patients.

What Does the Clinical Data Say?

SB-728-T is currently in Phase II trials, and Sangamo expects to report preliminary data in the first half of 2013, with full data by the end of the year. Sangamo reported early data for SB-728 in March 2012 (further data was reported in September 2012, more on that a bit later). Sangamo broke this trial into 2 arms: a group of 15 patients with CD4+ T-cell counts below 500, designated as Immune Non-Responders, and a group of 6 patients with cell counts above 450, designated as Immune Responders. After a month of treatment with SB-728-T, the Immune Responders group stopped taking antiretrovirals for 12 weeks. Sangamo stated that the viral loads of these 6 patients increased initially, as expected. However, 3 of 6 patients saw a 0.8 to > 2.0-log reduction in their viral loads, and one patient's viral load dropped to undetectable levels. According to Sangamo, this patient already had a CCR5Δ32 mutation. Sangamo stated that "control of HIV-RNA (suppression of VL) correlates significantly (p < 0.05) with calculated levels of circulating CD4+ T-cells that have undergone biallelic modification (i.e. modification of both copies) of the CCR5 gene. In this trial, SB-728-T showed only minor safety concerns, with the only reported symptoms being typical of those associated with infusion injections.

Sangamo reported updated Phase I data for SB-728 at the annual ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy) in September 2012. Sangamo reported that its Phase I dose-escalation study demonstrated that SB-728-T was well-tolerated, and resulted in what the company called "significant and sustained increases in CD4+ T-cells above baseline throughout the year-long period reported in the study." The increase in CD4+ T-cells was observed with a p-value of p < 0.038. Notably, 5 of 9 patients enrolled in the study showed CD4+ T-cell counts of greater than 500 cells/mm3, which is seen in the medical community as the threshold for starting HIV patients on highly active antiretroviral therapy (also known as HAART) (while guidelines published by the NIH suggest that even patients with cell counts above 500 begin antiretroviral therapy, they do not take into account the potential use of SB-728-T, and are based on the assumption that eventually, patients with cell counts above 500 will begin to see declines). Further analysis of the data done by Sangamo showed that proliferation of SB-728-T post-infusion was "sustained over the year-long period reported in the study with median modified circulating cell numbers measured to be 2.04-fold relative to input at 7 days, 0.96-fold at 6 months and 1.15-fold at 1 year post-infusion." Sangamo's Phase I data suggests that SB-728-T has the potential to reshape the immune systems of HIV patients, and allow them to fight back against the disease.

On the company's Q3 conference call, Sangamo's executives were pressed about this data, and what it means for the way forward. Wedbush argued that the FDA may not deem the data strong enough for approval given that SB-728-T does not completely wipe out the HIV virus. Analyst Liana Moussatos asked, "Based on the Phase I data, I thought it was very interesting about the treatment resulting in kind of normalizing the immune system in HIV infected patients where the virus had destroyed part of it. Is this, I mean in your discussion with the FDA, if SB-728-T treatment just restored the immune system and, say, reduces the strange cancers that result or the infections but maybe doesn't reduce viral load to nothing. Would that still be a viable treatment that could get approved?" Sangamo CEO Edward Lanphier and Geoff Nichol, the company's Executive Vice President of Research & Development, responded that this is a "hotly contested kind of question," stating that in the HIV/AIDS market, FDA approval has historically been based on viral load, which is the focus of the company's Phase II trials for SB-728-T, and that the company's goal is to render HAART unnecessary by keeping CD4+ T-cell counts above 500.

While SB-728-T does not destroy the HIV virus in every single patient, it has shown promising results, and 2013 will offer investors 2 different catalysts that can drive shares of Sangamo higher. The market for HIV and AIDS treatments is set to reach nearly $22 billion by 2018, therefore Sangamo has a tremendous opportunity to create meaningful value for its investors, as well as offer HIV patients a new treatment option, even if it captures only a minority of the market.

Financials & Pipeline Review

Sangamo ended Q3 2012 with $75.816 million in cash & investments (per its latest 10-Q filing), and expects to end 2012 with around $75 million in cash & investments. Sangamo's operating cash burn for the first 3 quarters of 2012 totaled $8.305 million, and even if Sangamo were to burn $10 million per quarter, the company would still have nearly 2 years of capital left to finance its operations.

While Sangamo is, unsurprisingly, unprofitable, the company does generate revenue ($4.907 million in Q3 2012, up 164.24% year-over-year, and $12.723 million for the first 3 quarters of 2012, up 128.38% from the first 3 quarters of 2011). Sangamo has licensing agreements for its technology in place with Sigma-Aldrich (SIAL), Dow Chemical's (DOW) AgroScience division, and Shire (SHPG). The company's agreement with Sigma-Aldrich involves the use of ZFP technology as a research reagent, while its agreement with Dow involves the use of ZFP technology in plant research. Sangamo's agreement with Shire, struck at the beginning of 2012, is the most crucial of these 3 agreements. Under the terms, Shire paid Sangamo $13 million upfront and received an exclusive worldwide license to ZFP technology for 4 different genes, covering blood clotting Factors VII, VIII, IX, and X. Shire also received rights to 3 other gene targets. Of the 6 pipeline programs (including SB-728-T) that Sangamo is currently working on, Shire owns ZFP technology in Huntington's disease and hemophilia.

In October, Sangamo and Shire presented the first set of pre-clinical data for their experimental treatment for Huntington's disease. The disease is caused by a mutation in a person's HTT gene, which is inherited from their parents. The HTT gene is responsible for encoding a protein also known as HTT. The mutation consists of a repeated stretch of DNA, known as a "CAG repeat." Under normal circumstances, a person's HTT gene has 10-29 of these CAG repeats. Patients with Huntington's disease, however, usually have more than 39. The more CAG repeats, the earlier the onset of symptoms, which include muscle and nerve degeneration, and loss of memory and cognitive control. Patients usually die within 10-20 years of symptom onset. Preclinical testing in animals has shown that lowering levels of HTT protein can slow, and potentially reverse the progression of Huntington's disease. Sangamo's pre-clinical data showed that the production of mutated HTT messenger RNA fell by more than 90%, all while leaving normal HTT cells and RNA untouched. The company expects to see this program in clinical trials by 2015. The companies' hemophilia program is also set to move into clinical testing.

Options Strategy, Takeover Prospects, and Conclusions

For Sangamo investors, gains or losses in 2013 will be driven by new data regarding SB-728-T. Fortunately, Sangamo has listed options, and they allow more conservative investors to mitigate some risk while preserving upside potential (prices are accurate as of the close of trading on Monday, January 14).

Sangamo Options Strategies, August 17, 2013 Expiration Date

   $7 Put   $8 Put   $7 Put & $11 Call
Stock Price   $8.20   $8.20   $8.20
Cost of Protective Put   $0.95   $1.50   $0.95
Proceeds from Sale of Covered Call   N/A   N/A   -$0.50
Net Cost per Share   $9.15   $9.70   $8.65
Maximum Loss   -23.50%   -17.53%   -7.51%
Maximum Profit   N/A   N/A   +27.17%
% Change Needed to Break Even   +11.59%   +18.29%   +5.49%

The August 17 expiration date is used because it encapsulates the first half of 2013, thereby allowing Sangamo investors to be protected through the company's first data release of SB-728-T, as well as giving them a chance to hold through the second data release. Of the options strategies listed above, the purchase of an $8 put is the most sensible. It caps losses at under 18% and requires a move of under 19% to be profitable, easily doable should Sangamo report positive data for SB-728-T. However, the 3 options strategies listed assume that investors have also purchased Sangamo stock outright. There is also another options strategy that I would like to highlight: the strangle. This strangle, also utilizing the August 17 options, involves purchasing the $2 call for $6.40 (giving an entry point of $8.40 per share, just 2.44% above where Sangamo is currently trading), as well as the $7 put for $0.95. The net cost is $7.35 per strangle, and it offers a similar level of protection as the options strategy outlined above, but with a smaller capital investment.

While there has been nothing substantial in the way of takeover rumors regarding Sangamo, there is always a possibility that a deal will occur given the company's cheap valuation in relation to the market that it targets. Just as GlaxoSmithKline (NYSE:GSK) did with Human Genome Sciences, Shire could move to take full control of Sangamo's pipeline. Alternatively, Gilead Sciences (NASDAQ:GILD) could strike a deal, although it would be motivated by different reasons. Gilead has delivered enormous profits to its investors by pioneering the treatment of HIV/AIDS; since going public in 1992, Gilead has returned almost 90,000% (Gilead has also helped enhance the lives of millions of patients). However, the fact that there is no cure for HIV/AIDS, and the fact that patients need continuous antiretroviral therapy to hold it at bay means that Gilead has much more stability than its biotechnology peers. However, should Sangamo and SB-728-T remove the need for such therapy, Gilead's business could be threatened. It is not unreasonable to assume that Gilead may make an offer Sangamo cannot refuse in order to protect its business. And with a market capitalization of less than $400 million, Sangamo is digestible for Gilead, even with a size-able premium. 2013 is poised to be a revolutionary year for Sangamo BioSciences, its investors, and HIV/AIDS patients.

Source: http://seekingalpha.com/article/1112651-sangamo-biosciences-a-potentially-revolutionary-2013?source=email_rt_article_readmore

The highlighted last paragraph is a bit concerning and could mean that if a takeover takes place, we, the patients will be the losers.
« Last Edit: January 15, 2013, 03:27:33 PM by xman »
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 freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #342 on: January 15, 2013, 04:20:41 PM »
Up another 7% today.

Things will get really fun when Sangamo and Paula Cannon start trials with ZFN modified haematopoietic (blood) stem cells in 2014.  If I remember correctly, these will then in theory produce armies of little modified CD4 cells with no CCR5 receptor.  Oh what fun that will be.
Beware Romanians bearing strange gifts

Offline geobee

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #343 on: January 15, 2013, 05:00:21 PM »
In 7 weeks at CROI we should know if SB-728 works -- whether Sangamo can get enough modified cells in you to drive the VL to be UD after the rebound from the STI. 

If they don't present VL data or say it's coming later in the year... well... I'd be tempted to cross this off of my "might be a cure" list.

They've touted (often) a durable increase in T-Cells (great!) -- but it's certainly not a functional cure.  If they can show a person/people who got the treatment, went on an STI, had an increase in VL, then a reduction to zero --well, that would be just incredible.   (I don't know why they'd even bother with the stem-cell trial at that point. )

If -- a BIG if -- it does work it'll be very interesting to know for whom it works (heterozygotes, initial T-Cells count, med regimens, etc.)  I'd also be *very* curious to know what percent of cells had to be modified to drive down the VL.

Also, it works, I think you'll hear a lot of people talking about changing the vector -- delivering the treatment through the adenovirus antibody excludes most people. And the test for it takes weeks, in which case you could have acquired it, which will render the treatment ineffective. 

If Sangamo is acquired, I don't this is necessarily a bad thing.  Generics are already threatening the profits of big pharma -- they need the next new thing.  (That's why they are looking so hard for cure drugs.)  Sangamo is a small -- they are going to need a larger company (or partnership) to help bring this to the clinic on a large scale if it works.

On a personal note, I've been poz for only 3 1/2 years and, after breathlessly searching for cure headlines for a year (OK, 2) have become much more sanguine re: "breakthrough" press releases. Still, the science behind this seems solid -- and we should know soon.   Interesting times.


Offline Dr.Strangelove

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #344 on: January 16, 2013, 08:06:25 AM »
I completely agree with all you said.

I really hope Sangamo will finally talk about viral load this time.

And yes, it wouldn't be unusual for Sangamo to be acquired by a bigger company. This happens all the time with small companies/startups that have a promising new drug in development.

I've been poz for less than 2 years. The research that is going on is exciting but I have no illusions. A 'cure' will not arrive overnight.

Offline Skydrake

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #345 on: January 16, 2013, 05:42:32 PM »
I completely agree with all you said.

And yes, it wouldn't be unusual for Sangamo to be acquired by a bigger company.

Maybe, but something is happening. Today its stocks topped the lists of Biggest Percentage Price Gainers among common stocks on the Nasdaq Stock Market.



Besides, tech investors are praising it:

http://seekingalpha.com/article/1112651-sangamo-biosciences-a-potentially-revolutionary-2013

Offline Jmarksto

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #346 on: January 16, 2013, 06:23:49 PM »
Maybe, but something is happening. Today its stocks topped the lists of Biggest Percentage Price Gainers among common stocks on the Nasdaq Stock Market.

Besides, tech investors are praising it:

http://seekingalpha.com/article/1112651-sangamo-biosciences-a-potentially-revolutionary-2013

I would like to see this technology work as much as the rest - however, I have learned that there is very often a wide gap between stock price and achieving market potential for "early entry" companies such as biotechs, clean energy, junior mining, etc.  The stock price of these small companies is subject to being whipsawed by institutional investors that run hot and cold, other investors that "pump and dump" (which is not a sexual reference), and a broader market of smaller investors that don't understand the science or the market. 

I am with geobee - show me the data on viral load and how it applies to the market (population) as a whole. Even then we have more trials to get through which will take more time and more money.

JM
03/15/12 Negative
06/15/12 Positive
07/11/12 CD4 790          VL 4,000
08/06/12 CD4 816/38%   VL 49,300
08/20/12 Started Complera
11/06/12 CD4   819/41% VL 38
02/11/13 CD4   935/41% VL UD
06/06/13 CD4   816/41% VL UD
10/28/13 CD4 1131/45%  VL 25
02/25/14 CD4   792/37%  VL UD
07/09/14 CD4 1004/39%   VL UD
11/03/14 CD4   711/34%   VL UD

Offline freewillie99

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #347 on: January 22, 2013, 07:43:52 PM »
Up another 6% to a 4x year high on 3x average volume.  Still no news.

Seems like someone thinks CROI will be interesting.
Beware Romanians bearing strange gifts

Offline blueballs

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #348 on: January 25, 2013, 12:13:44 PM »
Is this actually real or just another funding scam?

I stopped reading when I saw the word "AIDS virus". AIDS is not a virus, it's a syndrome even I know that and I don't work in medicine?

Offline Tadeys

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Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #349 on: January 25, 2013, 04:26:02 PM »
blueballs:

A little scepticism is OK when it comes to anything that is claiming a breakthrough. But a little online research also works wounders.

Is this a funding scam? No! Is it going to work in humans IS the question. There is a strong indication that it MIGHT be a revolution in AIDS treatment. Rumors are going around that Phase II results will be given in a few weeks at CROI. Fingers crossed.

-cheers

 


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