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Could the cure for death be made to be a virus?


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#1 lightowl

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Posted 13 May 2004 - 05:01 PM


I just read this article about some researchers coming up with a potential cure for AIDS that may be able to spread like a virus. Actually it is it self a virus. And it struck me. Could the cure for death be made to be a virus? And if so, could it be made to spread like the common flu? That would make immortality available to everybody, and fast.

http://www.wired.com...4,63441,00.html

#2

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Posted 31 May 2004 - 03:26 PM

It most certainly could. There is no faster known way to introduce genes into an existing adult genome other than via virus mediated transfection. Unfortunately, I suspect that the solution to aging is a multi-genetic one and would involve multiple gene modifications at precise locations. Even if we knew the genes responsible, present methods cannot guarantee the precise location of the inserted DNA sequence carried by the virus which is the reason gene therapy in general has been stalled for some time. It is only a question of either discovering another viral vector which is more particular in its insertion genome strategy or creating a heavily modified viral construct that is able to recognize discrete DNA sequences and insert itself accordingly. Only a question of time.

Another strategy of course would be to insert a self replicating plasmid that did not need genomic integration. But we may still need to silence one or more annoying genes, in which case we could use RNA interference.

My favorite strategy, mainly because it is the safest, is to use plasmid based gene expression. And as for what gene I would use - well if you have been following the "Aging and Evolution" debates - would be XP. This is the gene that when mutated causes xeroderma pigmentosum - an ailment associated with premature aging. The gene has a DNA repair function.

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#3 lightowl

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Posted 30 August 2004 - 08:59 AM

More promising viruses.

http://straitstimes....,269719,00.html

SCIENTISTS here have found a way to use a particular virus to reach and deliver therapy to damaged brain cells in patients suffering from Alzheimer's and Parkinson's disease.

Researchers at the Institute of Bioengineering and Nanotechnology (IBN) are relying on the prowess of viruses to get into cells and deliver healthy genes in order to reverse the effects of these debilitating diseases.



#4 olaf.larsson

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Posted 30 August 2004 - 04:27 PM

The problem is to make sure the dna is integrated in the genome in the right places. As I understand it expression of non human protein in cells could cause autoimmune problems, am I right?. It would be hard to find one vector which could infect all cells in the body. Has anyone done plasmid gene therapy yet? How you assure that the plasmid will distribute equally between dividing cells? Is the plasmid supposed to be integrated in some kind of virus to get in to the cells?

#5 lightowl

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Posted 30 August 2004 - 10:57 PM

I wish I could answer your questions, but I don't have the faintest clue. The thing that intrigues me is the prospect of cures for deceases that spread like a virus, but I am not at all sure these kinds of studies are on rout to that end. One big concern in of mine would be the risk of mutation in designer viruses that spread uncontrollably. But I am guessing that could be countered by some kind of mutation correction ability.

Here is more on the same study from BetterHumans.
http://www.betterhum...ID=2004-08-30-4

Besides their promise for treating neurological diseases, baculoviruses could also be used to trace neuronal pathways. By using a baculovirus that has been genetically modified for imaging purposes, for example, researchers could track the virus as it traveled a subject's central nervous system.


Another twist. Viruses as imaging tools. Wow. I wonder how long it will take before a complete neural network can be scanned and stored. ( and simulated and AI could be one giant step closer ). The spying implications would be immense if we could learn to interpret the neural connections. :)

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Posted 31 August 2004 - 12:05 AM

Wolfram:
1. No we cannot accurately control, at present, new DNA integration.
2. Autoimmune response is only a problem if you're expressing foreign peptides, not increasing expression of existing peptides.
3. Yes plasmid gene therapy has been demonstrated experimentally.
4. No, you cannot guarantee accurate distribution of plasmid
6. No, you do not have to have a viral delivery vehicle - even 'naked' DNA works

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#7 olaf.larsson

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Posted 31 August 2004 - 12:20 PM

Yeah this is so amazing I would love to do my PhD in gene therapy...

Lightowl. I can only thing of one mutation preventing mechanism: To make the virus consist of overlapping genes. Overlapping genes will cause that a mutation will affect two proteins and not one. If there is a mutation there is a much bigger chance that the virus is made inactive then if it would consist of normal non-overlapping genes.

Promoteus.

If exo peptide expression causes automimmunity we have to deal with this problem when expression for example various bacterial enzymes in cells as you proposed.

Are the plasmids supposed to be self replicating or not?

#8 lightowl

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Posted 14 February 2005 - 11:28 PM

Viruses as Cancer killers. This just keeps getting better and better.

The Cure for Cancer Might be: HIV
http://www.imminst.o...=ST&f=44&t=5372

#9 jaydfox

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Posted 14 February 2005 - 11:36 PM

Wow, good spot Lightowl. I forgot about this post, but in looking back, you were almost right on the money.

#10 apocalypse

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Posted 15 February 2005 - 01:55 AM

For an Anti-Aging treatment, I've been thinking it would be nice(later on) to make a heavily gm stem cell line that confers agelessness(and extensive regeneration capabilities would be nice too...), we can check that everything's a'Ok prior to insertion. Once inserted into the body they'd easily outcompete existing aging cells. Give'em immune privilege capability(from existing immune system, the stem cell line will either develop slightly modified immune cells that can bypass this particular measure-with slightly modified measure provided for next-gen creation of immune privilege sites- or make it so that it can be disabled-drugs/etc- in non-required places/tissues.). The developing new ageless immune system would swallow all problematic stuff, and could carry improved anti-cancer activity(like seen in some individuals).

The only thing that would be left is the brain, but given that individuals have been seen at 100+ with healthy minds, provided young glia, and a young circulatory system, and supporting organs, the transition may be adequate/gradual enough.

#11 dangerousideas

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Posted 15 February 2005 - 04:28 AM

REOLYSIN® is a viral treatment that appears to be effective against 2/3 of all cancers, and is also apparently useful as a radiation sensitizing and chemo sensitizing agent in the other 1/3. Prefered mode of delivery will be Systemic IV. It is utterly safe, and has no adverse side effects. I would be very surprised if it does not eventually become a treatment of choice for cancer. FULL DISCLOSURE: I have been following - and invested - in this company for 5 long, long, (long) years. But I am more convinced than ever that it is the real deal. If you don't already know about this approach then you want to - trust me!

This company is notorious for bland understatement. Nobody knows why. When you do your own DD you will see that the real story is much more exciting than it looks here...

From the Company Website (emphasis mine) Oncolytics Biotech
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Oncolytics' technologies are based on discoveries arising from research conducted at the University of Calgary. Dr. Matt Coffey, Chief Scientific Officer for Oncolytics, was instrumental in these discoveries and continues to play a pivotal role in the product development process.

REOLYSIN®, the company's proprietary formulation of the human reovirus, has been demonstrated to replicate specifically in tumour cells bearing an activated Ras pathway. Activating mutations of Ras and upstream elements of Ras may play a role in greater than two thirds of all human cancers. REOLYSIN® may represent a novel treatment for Ras activated tumour cells and some cellular proliferative disorders.

Reovirus, an acronym for Respiratory Enteric Orphan virus, is generally believed to inhabit the respiratory and bowel systems in humans. Reovirus is found naturally in sewage and water supplies. By age 12, half of all children show evidence of reovirus exposure and by adulthood, most people have been exposed. However, the disease is non-pathogenic, meaning there are typically no symptoms from infections. The link to its cancer-killing ability was established after the reovirus was discovered to reproduce well in various cancer cell lines.

Tumours bearing an activated Ras pathway are deficient in their ability to activate the anti-viral response mediated by the host cellular protein, PKR. Since PKR is responsible for preventing reovirus replication, tumour cells lacking the activity of PKR are susceptible to reovirus replication. As normal cells do not possess Ras activations, these cells are able to stop reovirus infection through normal PKR activity. In tumour cells with an activated Ras pathway, reovirus is able to freely replicate and eventually kill and host tumour cells. As cell death occurs, progeny virus particles are then free to infect surrounding cancer cells. This cycle of infection, replication and cell death is believed to be repeated until there are no longer any tumour cells carrying an activated Ras pathway available.

The activation of the Ras pathway can be mimicked in non-cancerous cells by treating these cells with the chemical 2-aminopurine (2-AP) which prevents the activation of PKR.

REOLYSIN® for the Treatment of Ras Mediated Tumours
Because the reovirus kills cancer kills with an activated Ras pathway, REOLYSIN® is a potential therapeutic for up to two thirds of all human cancers, including, but not limited to, malignant glioma, pancreatic, colon and some lung cancers.

Phase I Clinical Trial Results
In an initial Phase I study, late-stage cancer patients who had failed all other therapies received either a single or three injections of REOLYSIN® directly into a large, subcutaneous tumour. The dosage ranged from 107 PFUs to 1010 PFUs.

None of the patients receiving REOLYSIN® experienced any serious adverse events related to the virus, nor were there any dose limiting toxicities. Tumour responses were measured at both the treated lesion as well as remote tumour sites. Evidence of viral activity was detected in 11 of 18 patients (61%) with the tumour regression ranging from 32% to 100%. (Viral activity is defined as a transitory or lasting tumour regression of at least 30% measured in two dimensions against the tumour size prior to injection on the first day of treatment)

T2 prostate cancer trial
In Spring, 2002, Oncolytics initiated a clinical trial examining the use of REOLYSIN® in cancer confined to the prostate gland. The primary endpoints of this study were to examine safety and the histopathology of prostate tissue post-therapy and post-prostactectomy. Patients were treated with a single injection of REOLSYIN® directly into the prostate gland. Final results showed evidence of apoptotic tumour cell death in four of six patients, with no safety concerns. A fifth patient saw PSA level drop by 53% and the prostate gland shrank by 67% from just prior to injection to surgical removal of the prostate gland three weeks later.

Phase I/II recurrent malignant glioma trial
In summer, 2002, Oncolytics initiated a Phase I/II clinical trial examining the use of REOLYSIN® in recurrent malignant glioma, one of the deadliest forms of brain cancer. The primary endpoint of the Phase I component of this study is safety; a secondary endpoint is to examine lifespan extension. Patients are treated with a single injection of REOLYSIN® directly into the brain tumour. Interim safety results from the first six patients show there were no safety concerns with injecting REOLYSIN® intracerebrally.

Systemic administration trial
In May, 2004, the Company announced that the first patient had been enrolled in its sytemic administration trial in the United Kingdom. The primary objective of Oncolytics' first systemic administration study is to determine the safety of REOLYSIN® when administered intravenously. The secondary objective is to observe tumour and immune system response to intravenous infusion of REOLSYIN®, which will help to determine dosage levels in subsequent clinical studies. A maximum of 40 patients with advanced stage, primary or metastatic solid tumours who have failed all other cancer therapies will be enrolled at the Royal Marsden Hospital and St. George's Hospital in the United Kingdom.

Other trials
In October, 2003, Oncolytics Biotech signed a collaborative agreement with the National Cancer Institute to conduct multiple clinical trials with REOLYSIN®. As more information about these trials becomes available, it will be posted to this website.

----
Dangerous...

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#12 jaydfox

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Posted 17 February 2005 - 07:16 PM

Apocalypse, that's a good idea, and one that's very similar to other aging treatments that have been suggested, including SENS. SENS would rely on stem cell reseedings that would replenish all body tissues's cells, as all body tissues would experience a "turnover" of most, if not all, of their cells every decade, or at most once every "adult lifetime", i.e. 50 years or so.

The main drawback is the brain, as we still don't know enough to be able to safely replace every brain cell in even as long a period as a lifetime. Fixing the brain will be a challenge, as we may have to find ways to fix the existing cells, rather than just replacing them.

How "turnover" is achieved is still being disputed, but De. de Grey's WILT is one such possibility.




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