A potential cure for HIV - manipulating the human genome

[Da_Latios]

"Junk DNA" are inactive parts of your genome, switched off long ago in evolutionary history. Now scientists say there's a junk gene that fights HIV. And they've discovered how to turn it back on.

 

 

 

What these scientists have done could give us the first foolproof HIV vaccine. They have re-awakened the human genome's latent potential to make us all into HIV-resistant creatures. This evening in PLoS Biology, they've published their ground-breaking research.

 

 

 

A group of scientists led by Nitya Venkataraman and Alexander Colewhether wanted to try a new approach to fighting HIV - one that worked with the body's own immune system. They knew Old World monkeys had a built-in immunity to HIV: a protein called retrocyclin, which can prevent HIV from entering cell walls and starting an infection. So they began poring over the human genome, looking to see if humans had a latent gene that could manufacture retrocyclin too. It turned out that we did, but a "nonsense mutation" in the gene had turned it off at some point in our evolutionary history.

 

 

 

Nonsense mutations are caused when random DNA code shows up in the middle of a gene, preventing it from beginning the process of manufacturing proteins in the cell. Venkataraman and her team decided to investigate this gene further, doing a series of tests to see if the retrocyclin it produced would keep HIV out of human cells. It did.

 

 

 

At last, they knew that if they could just figure out a way to reawaken the "junk" gene that creates retrocyclin in humans, they might be able to stop HIV infections. The researchers just needed to figure out a way to remove that nonsense mutation and get the target gene to start manufacturing retrocyclin again.

 

 

 

Here's where things really get interesting. The team found a way to use a compound called aminoglycosides, which itself can cause errors when RNA transcribes information from DNA to make proteins. But this time, the aminoglycoside error would work in their favor: It would cause that RNA to ignore the nonsense mutation in the junk gene, and therefore start making retrocyclin again. In preliminary tests, their scheme worked. The human cells made retrocyclin, fended off HIV, and effectively became AIDS-resistant. And it was done entirely using the latent potential in the so-called junk DNA of the human genome.

 

 

 

After more research is done, the researchers believe this might become a viable way to make humans immune to HIV infection.

 

 

 

What intrigues me, beyond the amazing idea of an AIDS vaccine, is that aminoglycosides have the potential to unlock the uses for other pieces of junk DNA. Those of you who read Greg Bear's novel Darwin's Radio know that this scenario is familiar scifi territory: In that book, humans start rapidly evolving after their junk DNA re-awakens in response to stress. Could we induce instant mutations, or gain other new immunities by using aminoglycosides on our junk DNA? What would it mean to have the whole crazy, giant human genome at our command?

 

 

 

via PLoS Biology

 

Source: http://io9.com/5227470/a-drug-to-re%20awaken-ancient-human-genes-and-fight-hiv

 

 

 

What do you think? Could this be the real thing?

 

Perhaps in 50 years we could all be telekinetic cyborgs, too.

[warri0r45]

It's certainly some ingenuitive molecular biology. Here's another source:

 

 

 

Despite decades of effort, medical science hasn't yet succeeded in preventing or curing infections by human immunodeficiency virus (HIV), the virus that causes AIDS. The virus's rapid mutation rate has so far prevented the creation of a vaccine, leaving the medical community to fight individual infections with drugs that inhibit viral replication. These drugs, while effective, are not a cure. Additionally, they're costly, have serious side-effects, and must be administered for life. So, the search continues for other approaches to help prevent new infections, and to treat or cure existing ones. In this issue of PLoS Biology, Nitya Venkataraman, Alexander Cole, and colleagues describe one of these new approaches: awakening a latent defense mechanism in human cells.

 

 

 

Venkataraman et al. focused their work on retrocyclin, a member of the defensin family of proteins. Defensins are made by all primates and have potent anti-microbial activity. Retrocyclin was recently shown to strongly inhibit HIV entry into human cells by blocking the interaction of viral proteins with their cellular receptors. Unfortunately, although the retrocyclin protein is found in Old World monkeys and orangutans, it is not present in humans (or gorillas and chimps), even though we have the retrocyclin gene.

 

 

 

That's because the human retrocyclin gene contains a mutation, known as a nonsense mutation, that prevents the production of the encoded protein. Nonsense mutations are a common cause of many human hereditary diseases, including cystic fibrosis, some cancers, and muscular dystrophies. They work by disrupting the genes that contain the instructions for making specific proteins. Information in genes, encoded in nucleotide triplets called codons, is preserved as the DNA sequence is transcribed into the RNA molecules that carry it to the cell's protein factory, the ribosome. Ribosomes read the order of the nucleotides within codons to determine which amino acids (protein building blocks) should be incorporated into a protein, and in what order. When a ribosome encounters stop codons, it dutifully stops adding amino acids to a protein. Nonsense mutations change an amino acidencoding codon into a premature stop codon, resulting in a truncated proteinor no protein at allbeing made.

 

 

 

No one knows how or why humans acquired a nonsense mutation in the retrocyclin gene. But, since monkey retrocyclin has the ability to block HIV infection, Venkataraman et al. decided it would be worth investigating whether the human version of the protein is similarly useful. Almost immediately, they encountered a potential problem: even if modern human cells had a functional copy of the gene available, they may not be able to make retrocyclin protein. That's because the monkey retrocyclin protein has an unusual 3D structure that is unique. The production of retrocyclin protein might require some specialized mechanism, which could be absent in humans.

 

 

 

To determine whether human cells have retained the capacity to make retrocyclin protein, Venkataraman et al. corrected the premature stop codon mutation in a copy of the human retrocyclin gene. Next, they inserted the corrected gene into human promyelocytic cells, and looked to see if protein was produced from the gene. They found that cells harboring the corrected gene could make a protein similar to the monkey version of retrocyclin. But could human retrocyclin block HIV infection? Indeed, extracts made from cells containing the corrected gene could reduce HIV growth, and so could the retrocyclin protein purified from these extracts. Collectively, these results suggest that human cells have a potentially importantbut latentmechanism to protect against HIV.

 

 

 

If retrocyclin could be restored in humans, it might make a difference in the fight against HIV. The authors therefore wondered if it would be possible to make human cells ignore the premature stop codon in the retrocyclin gene. To accomplish this, they turned to aminoglycosides, compounds known to make human cells ignore premature stop codons. Aminoglycosides are normally used to fight off bacterial infections; they work by binding tightly to bacterial ribosomes, blocking their protein-making capacity. These compounds can also bind to human ribosomes, but they do so much more weakly. Therefore, they don't block protein creation in human cells but cause ribosomes to make occasional errorslike missing stop codons. The authors found that treating human cells with aminoglycosides allowed the cells to make retrocyclin at sufficiently high levels to inhibit infection by HIV. Importantly, the authors showed that antibodies specific to retrocyclin could destroy the HIV-blocking activity of aminoglycoside-treated cells, indicating that the anti-HIV activity of aminoglycoside-treated cells mediates their new ability to produce retrocyclin.

 

 

 

Might aminoglycosides, or drugs like them, be useful in rallying this ancient defense mechanism to battle against HIV? Much more work would be needed to demonstrate the safety and effectiveness of this approach for stimulating retrocyclin production, and to investigate whether this could actually protect people from HIV. But these findings represent a promising step in that direction.

 

 

 

http://www.pubmedcentral.nih.gov/articl ... id=2672611

 

 

 

The last paragraph is where my concern lies - safety. I wonder what other latent pseudogenes aminoglycosides will activate. What effects will all of those proteins have on the cell? Plenty of more research is required before this becomes a cure, that's for sure.

 

 

 

Edit: Here's the actual paper: http://www.pubmedcentral.nih.gov/articl ... id=2672613

[sohkmj1]

Won't the HIV, I dunno, mutate to counter this?

[mmmcannibalism]

Won't the HIV, I dunno, mutate to counter this?

 

 

 

depending on how this works that might be a very hard defense to mutate around; if it does manage to completely block aids spreading then the virus wouldnt be able to have the most resistant parts replicate.

[Bauke]

Mutation is random, you just don't know. It also depends on how solid the defense mechanism of the human body is against the HIV as is pointed out above. Mutation can't work miracles. The problem with antiviral therapies is that they're usually quite virus specific. In such a case, only a small mutation is required to circumvent the therapy. The proposed treatment in this paper might just be more solid. But much, much more research is needed, and we're probably still years away from any concrete therapies based on this research.

[EdgedThesis]

 

 

 

The last paragraph is where my concern lies - safety. I wonder what other latent pseudogenes aminoglycosides will activate. What effects will all of those proteins have on the cell? Plenty of more research is required before this becomes a cure, that's for sure.

 

 

 

Edit: Here's the actual paper: http://www.pubmedcentral.nih.gov/articl ... id=2672613

 

 

 

Spot-activation is impossible?

 

I know several genes act as activators for the transcription of others, but did the paper say that any protein but retrocyclin will be produced?

[fastortoise]

Edit: Here's the actual paper: http://www.pubmedcentral.nih.gov/articl ... id=2672613

 

Seems interesting. I'm currently too busy to read an entire first source research paper, but it's because i'm studying for a genetics exam :lol: I'll get to it tomorrow night.

 

As for the concept of this study.. i'm skeptical.

[BlackDawn]

I call zombies.

 

 

 

It sounds pretty promising though, if this succeeds then all of those sex crazed teens will have second chances... Or they'll return to their lives of unprotected sex.

[Madmanpur3]

I don't see why so much money and so many resources are being put towards the "fight against AIDS/HIV" when we already have methods of prevention that prove essentially 100% effective.

 

 

 

1. Don't do drugs that require needles (and if you ignore this and do, make sure they are clean needles).

 

2. Don't have random sex.

 

3. Don't let idiots deal with the blood in hospitals.

 

*credit to a friend of mine for that list*

 

 

 

Personally I'd rather see all this attention put towards AIDS/HIV to go towards other diseases which we cannot prevent so easily. Honestly, in most cases it's the person's own fault that they have it.

[Range_This11]

I don't see why so much money and so many resources are being put towards the "fight against AIDS/HIV" when we already have methods of prevention that prove essentially 100% effective.

 

 

 

1. Don't do drugs that require needles (and if you ignore this and do, make sure they are clean needles).

 

2. Don't have random sex.

 

3. Don't let idiots deal with the blood in hospitals.

 

*credit to a friend of mine for that list*

 

 

 

Personally I'd rather see all this attention put towards AIDS/HIV to go towards other diseases which we cannot prevent so easily. Honestly, in most cases it's the person's own fault that they have it.

 

There are people that go around with contaminated needles and just stab people in a club setting. There was a guy who did it in Minneapolis earlier this year. And there are those that lie about having an STD to you.

[Madmanpur3]

[hide=quote]

I don't see why so much money and so many resources are being put towards the "fight against AIDS/HIV" when we already have methods of prevention that prove essentially 100% effective.

 

 

 

1. Don't do drugs that require needles (and if you ignore this and do, make sure they are clean needles).

 

2. Don't have random sex.

 

3. Don't let idiots deal with the blood in hospitals.

 

*credit to a friend of mine for that list*

 

 

 

Personally I'd rather see all this attention put towards AIDS/HIV to go towards other diseases which we cannot prevent so easily. Honestly, in most cases it's the person's own fault that they have it.

[/hide]There are people that go around with contaminated needles and just stab people in a club setting. There was a guy who did it in Minneapolis earlier this year. And there are those that lie about having an STD to you.

I did say most to account for hospital misshaps as well as drive-by pokings, but as far as I'm concerned the ones who get lied to are still largely at fault, unless they are in a serious relationship with said liar. As such, I still stand by my statement of "most cases it's the person's own fault that they have it".

[fastortoise]

[hide=quote]

I don't see why so much money and so many resources are being put towards the "fight against AIDS/HIV" when we already have methods of prevention that prove essentially 100% effective.

 

 

 

1. Don't do drugs that require needles (and if you ignore this and do, make sure they are clean needles).

 

2. Don't have random sex.

 

3. Don't let idiots deal with the blood in hospitals.

 

*credit to a friend of mine for that list*

 

 

 

Personally I'd rather see all this attention put towards AIDS/HIV to go towards other diseases which we cannot prevent so easily. Honestly, in most cases it's the person's own fault that they have it.

[/hide]There are people that go around with contaminated needles and just stab people in a club setting. There was a guy who did it in Minneapolis earlier this year. And there are those that lie about having an STD to you.

I did say most to account for hospital misshaps as well as drive-by pokings, but as far as I'm concerned the ones who get lied to are still largely at fault, unless they are in a serious relationship with said liar. As such, I still stand by my statement of "most cases it's the person's own fault that they have it".

 

1. Problems are inevitable

 

2. Problems are solvable

 

Why go on about preventing AIDS when it obviously cannot be contained?

[Giordano]

What about those who were born into having AIDS? Recent newborns whose one of their parents have AIDs and now they have it.

 

 

 

Besides, if we can find a way to combat this rapid-mutating virus, we can roughly use the same knowledge to fight other possible viruses like HIV in the future.

[Guest]

I don't want to have my DNA screwed around with, thanks :|

 

 

 

of course, if we get a few hundred test dummies first....

[warren211]

I think I'm gonna stick to abstinance for now, just because it's a new cure. I really hope this doesn't get into every young kid's head "oh, they're coming close to a cure for HIV. I can have sex now". But in my Biology class we were just discussing the possibilities of uses for non-coding parts of the genome, and apparently this is what can happen. It's amazing, the new uses of the human genome discovered every so often. I hope this can lead to a promising cure to HIV some day.

[Wisp]

The problem with this, is we don't fully understand the human genome. A seemingly useless, ancient gene, could affect some other gene, and if altered could mess a lot of things up.

 

If you don't want AIDS, don't be stupid. If you're gonna have sex with people you aren't sure about, use a condom. Not 100% effective, but it's the best you can do.

[Madmanpur3]

[hide=quote]

I don't see why so much money and so many resources are being put towards the "fight against AIDS/HIV" when we already have methods of prevention that prove essentially 100% effective.

 

 

 

1. Don't do drugs that require needles (and if you ignore this and do, make sure they are clean needles).

 

2. Don't have random sex.

 

3. Don't let idiots deal with the blood in hospitals.

 

*credit to a friend of mine for that list*

 

 

 

Personally I'd rather see all this attention put towards AIDS/HIV to go towards other diseases which we cannot prevent so easily. Honestly, in most cases it's the person's own fault that they have it.

[/hide]There are people that go around with contaminated needles and just stab people in a club setting. There was a guy who did it in Minneapolis earlier this year. And there are those that lie about having an STD to you.

I did say most to account for hospital misshaps as well as drive-by pokings, but as far as I'm concerned the ones who get lied to are still largely at fault, unless they are in a serious relationship with said liar. As such, I still stand by my statement of "most cases it's the person's own fault that they have it".

1. Problems are inevitable

 

2. Problems are solvable

 

Why go on about preventing AIDS when it obviously cannot be contained?

So let those that don't care enough to self-prevent it deal with it. Why should we make their mistake our problem?

[Tim]

Oh joy, more teens running around trying to have sex with every walking object in human shape. Thankfully it doesn't stop them getting pregnant, always gotta be a cost for stupidity.

 

 

 

Oh, I call upon Zombies for this.

[deathdrow]

I wish I understood genetics better, then I'd get how this works.

 

aids=good.

[Kenshinjapan]

Wasn't this a topic like 6 months ago?

[Madmanpur3]

No, that topic was discussing the possibility of having the virus mutate itself to death - must not have worked out. :P

[fastortoise]

[hide=quote]

I don't see why so much money and so many resources are being put towards the "fight against AIDS/HIV" when we already have methods of prevention that prove essentially 100% effective.

 

 

 

1. Don't do drugs that require needles (and if you ignore this and do, make sure they are clean needles).

 

2. Don't have random sex.

 

3. Don't let idiots deal with the blood in hospitals.

 

*credit to a friend of mine for that list*

 

 

 

Personally I'd rather see all this attention put towards AIDS/HIV to go towards other diseases which we cannot prevent so easily. Honestly, in most cases it's the person's own fault that they have it.

[/hide]There are people that go around with contaminated needles and just stab people in a club setting. There was a guy who did it in Minneapolis earlier this year. And there are those that lie about having an STD to you.

I did say most to account for hospital misshaps as well as drive-by pokings, but as far as I'm concerned the ones who get lied to are still largely at fault, unless they are in a serious relationship with said liar. As such, I still stand by my statement of "most cases it's the person's own fault that they have it".

1. Problems are inevitable

 

2. Problems are solvable

 

Why go on about preventing AIDS when it obviously cannot be contained?

So let those that don't care enough to self-prevent it deal with it. Why should we make their mistake our problem?

 

I don't see how you can blame people for getting AIDS in non-developed countries. Do you honestly believe Africans could have walked over to the corner store and buy a pack of condoms? Or maybe you just don't care about them or their lifestyle. This obviously doesn't only apply to Africa, but that entire continent does have an enormous death toll from AIDS alone, especially when combined with Malaria. You can be sure that the majority of the population that has AIDS aren't little teenagers fooling around.

 

 

 

Yes, my anti-preventing view does have a basis, which is that every attempt to prevent some sort of sickness or life threatening problem never works the way it's supposed to. We're better off just finding a cure asap. If you can demonstrate one major global problem that has been resolved just by prevention, I may consider leaving the AIDS battle at the condom/abstinence level.

 

 

 

If they fix all sexually transmitted diseases, maybe sex won't be frowned upon so much anymore... Sorry if my post did not make sense in some bits, it's 1:28 AM & I ought to be in bed.

[warri0r45]

 

 

 

The last paragraph is where my concern lies - safety. I wonder what other latent pseudogenes aminoglycosides will activate. What effects will all of those proteins have on the cell? Plenty of more research is required before this becomes a cure, that's for sure.

 

 

 

Edit: Here's the actual paper: http://www.pubmedcentral.nih.gov/articl ... id=2672613

 

 

 

Spot-activation is impossible?

 

I know several genes act as activators for the transcription of others, but did the paper say that any protein but retrocyclin will be produced?

 

 

 

What's spot activation?

 

 

 

I haven't read the entire paper (just abstracts and introduction), but as far as I'm aware aminoglycosides have no way of discriminating between transcripts. In other words, other pseudogenes that produce a transcript may become active by virtue of their reactivated stop codons. I don't see the link with transcription factors... unless you're saying some transcription factor pseudogene could become active through this technique and screw up the transcription of other genes?

[Shiny]

Forget a swine flu cure, this is much better.

[trapical]

No, no, no, no, no.

 

 

 

This will never happen, the most basal rule any geneticist leans is never, NEVER, NEVER manipulate the DNA of humans. I mean, i can't stress this enough. The North Koreans and Iranians even follow this rule, and for good reason. Regular medicine like surgery is fine, if you screw up the person dies, no big deal. If you screw up with someone's DNA they leave your office carrying the DNA, and that mutated DNA is now in the general population. They can have kids, etc, and mankind's genome will forever be tainted. It took us billions of years to get to the point where we are genetically, trillions of humans/apes have died to evolve us to this point. If we start "activating genes" or what not, genes that we evolved to leave inactive, we screw up everything our species has lived and died for. I mean, look what we did to the wheat crops, 100 years ago their were thousands of species of wheat. Now we have about four, and a single virus can wipe out an entire species since we removed genetic diversity to increase crop yeilds.

 

 

 

Trust me, no scientist will ever even remotely consider doing DNA work in humans. It really would be like asking a historian to burn down the library of congress.