Tag Archives: human immunodeficiency virus

Human Genome Tinkering Could Be Our Best Bet to Beat HIV

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The human immunodeficiency virus (HIV) is a crafty little beast, constantly mutating to mask itself from our body’s defenses, but always entering cells through the same molecular door. The design of that cellular door is governed by our DNA, so why not change the lock by modding our genetic code?

In 2006, a minor medical miracle occurred. HIV-positive leukemia patient Timothy Ray Brown—the second Berlin Patient—received a bone marrow transplant that saved his life in more ways than one. The marrow that he received was from a donor with a unique double mutation to a gene on the 3rd chromosome known as CCR5. This gene codes for the surface protein that the HIV virus uses to gain entry into our white blood cells (specifically, CD4+ T-cells); however the double mutation shuts down these sites and provides a natural immunity to HIV. This mutation is exceptionally rare, only occurring in about one percent of Caucasians and nowhere else. It’s been hypothesized that it’s this same natural immunity that allowed a small portion of Europeans to make it through the Black Plague unscathed.

While that was fantastic news for Brown, who nearly a decade later remains off of his retroviral drug regimen and maintains an undetectable level of the virus in his system, it’s not of much use to the rest of us. With both the mutation prevalence and bone marrow compatibility matches in general being so rare, there was no effective means of using transplants as delivery vectors for this beneficial genetic condition. And it’s worth noting that the very process of becoming HIV-free nearly killed Brown. But that’s where Professor Yuet Kan’s team at UCSF comes in.

Kan figured that if integrating this double mutation wouldn’t work on the macro level—that is, replacing a patient’s bone marrow with that of a naturally HIV-immune person’s—maybe it would at the molecular level, thereby allowing researchers to confer the benefits while cutting out the marrow donation. To that end, he and a team of researchers from the University of San Francisco are employing cutting-edge genetic editing techniques to snip out the beneficial length of DNA coding and integrate it with a patient’s own genome.

The technique they’re using is known as CRISPR (Cas9) genome-editing. CRISPRs, (clustered regularly interspaced short palindromic repeats) are DNA delivery vectors that replace the existing base codes at a specific part of a specific chromosome with new base pair sets. Cas9, on the other hand are the “molecular scissors” that Kan’s team employs to first cut out the offending DNA. It sounds easy, sure—just find the string of DNA you want to replace, then snip it out with Cas9 DNA scissors, and install some new DNA using a CRISPR—however the nuts and bolts of the process are far more technically challenging.

The patient’s own blood cells would be employed as a precursor. Researchers would then have to convert those cells into induced pluripotent stem (iPS) cells by modulating a number of genetic switches, thereby instigating their regression to more basic stem cells. After that, the offending CCR5 gene would need to be knocked out and replaced with the better, double-mutated version before the now fortified blood cells were transfused back into the patient. Not only is there no chance of the body rejecting the new cells (they are the patient’s own after all), the technique also neatly sidesteps the whole embryonic stem cell issue.

While the technique is still in its early stages of development and no human trial dates have yet been set, it holds huge promise. Not just for the 35 million people annually infected by HIV, but also sufferers of sickle cell anemia and cystic fibrosis—two deadly diseases caused by a single protein deformation—could benefit from similar techniques. By figuring out which genes do what on our iPS cells, we could even theoretically grant everyone on Earth immediate immunity to any number of diseases.

Of course, being able to update and augment our genetic code opens up a whole slew of potential concerns, objections, and abuses. Just look at the ire raised over the use of embryonic stem cells in the early 2000s. People were lost their minds because they thought scientific progress was being built on the backs of fetuses. Researchers had to go and invent an entirely new way of making stem cells (the iPS lines) just to get around that one moralized sticking point, so you can bet there will be plenty of chimera, master race, and Island of Dr. Moreaureferences bandied about should we ever begin seriously discussing the prospect of upgrading our genes. And could certainly slow progress in this specific research.

That’s not to say that the hysteria that accompanies seemingly every news cycle these days is completely off base. Like cars, styrofoam, pressure cookers, and thermonuclear bombs, this technology can be used for evil just as easily as it can be for good. And while we’re not nearly as genetically complex as, say, an ear of corn, wrangling the myriad of interactions between our various genes is still an incredibly complex task and one with severe consequences should something go awry—even if we can avoid creating unwanted mutations through stringent testing and development methodology as we do with today’s pharmaceutical development. So why not turn ourselves into the ultimate GMOs? It certainly beats everyone becoming cyborgs.

Article via Gizmodo

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The quest for a HIV vaccine

Credit: UNAIDS

There is broad scientific consensus that getting to zero new HIV infections will require an HIV vaccine. Modelling shows that even a partially effective HIV vaccine can save many lives and dollars over time.

Although a vaccine to prevent HIV could be the tool to quicken the pace to reach the end of AIDS, the quest for an effective vaccine has until now proved elusive. The very nature and variety of the human immunodeficiency virus has meant that it has resisted most attempts to quell its spread and scientists and vaccinologists the world over are focusing efforts on finding solutions.

Exciting recent developments in HIV vaccine research are instilling hope around finding an effective vaccine. In 2009, results from a trial in Thailand—RV144—showed a 31.2% vaccine efficacy in preventing HIV infections. Although only modestly protective, the results instilled new hope that an HIV vaccine could be found and made available for populations around the world most in need of a vaccine.

The results represented a significant scientific advance, and were the first demonstration that a vaccine can prevent HIV infection in a general adult population. It was a discovery of great importance and has been followed by more encouraging data in the last couple of years.

Data presented in the past year has been presented on the protective immune responses that were stimulated by the Thai vaccine trial.  Trials are now planned to see if an RV144-like regimen will protect against a strain of HIV infection found in South Africa and against HIV acquisition by people at higher risk of exposure, specifically men who have sex with men.

UNAIDS and the US Centers for Disease Control worked closely with modelling teams to estimate the impact of the RV144 regimen in different countries and with different populations and found that 10% of infections could be prevented if the same 31% efficacy was found in people who receive the vaccine. This shows that a modestly effective HIV vaccine could add to the prevention toolbox of partially effective methods, hastening the decline of the HIV epidemic.

These and other advances in HIV vaccine development—including the design of new tools and technologies for vaccine delivery—have boosted optimism in the field about the prospects for the development of a safe and effective AIDS vaccine.

However, early data from the HIV Vaccines and Microbicides Resource Tracking Working Group is showing that a downturn in HIV vaccine funding that began in 2008 continued through 2011. The quest for effective HIV vaccines is a long-term investment in both the product (vaccines) and in the people who will develop, produce, market and support them. Investments in research and trials are essential and can bring benefits far beyond the AIDS field.

The need for a vaccine to prevent HIV is clear.  There are in excess of 34 million people living with HIV, and every day more than 7000 people are becoming newly infected with the virus. Although a vaccine may not provide the magic bullet to end the AIDS epidemic, it would provide an additional tool to add to the robust package of HIV prevention options which are now available.

UNAIDS will continue to work with multiple partners––scientific communities, national and international AIDS research agencies, the pharmaceutical industry, private foundations, member states, and affected communities––to push the HIV vaccine agenda forward and ensure that the quest for a safe and effective HIV vaccine continues.

Original Article via UNAids

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Cannabinoid Receptors Give Cells The Tools They Need To Defend Against HIV Infection

Researchers have reported that when healthy cells were placed in a sample dish with the human immunodeficiency virus (HIV), along with a dose of cannabinoids, the cells, which normally would rather quickly become infected, simply denied entry to the virus, and responded as if it were not a threat at all.

The cannabinoids themselves don’t act anti-virally. They are not responsible for killing the virus, the tissue sample takes that claim. The cannabinoids stimulate a part of the cells that bears an endogenous resemblance to the chemical structure of the cannabinioids themselves. Pairing between naturally occurring substances and receptors in the human brain works the same way as the formation of anti-bodies does; contact evokes adaptation in the receptors, causing them to bear an imprint of the experience. It is unknown if these receptors exist in cells because of the inclusion of the cannabis plant in the diets and pharmacopoeia of earlier human ancestors. In any case, receptors that are designed to respond to cannabinoids are found in the cell structure of every human. When the receptors were stimulated in the tissue culture, in rate of infection by the HIV virus was greatly impeded.

The stimulation of the receptors wasn’t just detrimental to HIV, it increased the cells abilities to defend itself against any number of viruses and bacteria. This has a great amount of potential for individuals experiencing the more advanced stages of HIV infection.

The use of cannabinoids might be able to provide these patients with much needed assistance with defending themselves against viral attack, without draining them of all other reserves.

Successful studies in apes
Surprisingly, at the beginning of the experimentation, the researchers had expected the application of cannabis’ THC to increase the speed at which the HIV took hold, and so it came as a general shock when the cannabinoids not only didn’t foster the virus’ strength, but also attenuated the symptoms that are generally associated with the infection. While ethics laws prevent these tests from being conducted in humans, a nearly identical virus, which is thought to be the original source of the human immunodeficiency virus, exists in other species of great ape, called the simian immunodeficiency virus, or SIV. Tests indicate that SIV is inhibited by cannabinoids, and the progression and mortality rates are greatly reduced.

Brief studies on humans have been limited to verification that inhalation of cannabis smoke, on of the treatments that HIV patients may rely on for pain relief, had no noticeable detrimental effects with regards to the potency of HIV.

Article Sources
http://www.plosone.org
http://www.enewspf.com
http://norml.org

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