Tag Archives: Crispr

Chinese Researchers Experiment with Making HIV-Proof Human Embryos

Yes, you read that headline correctly!

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Chinese fertility doctors have tried to make HIV-proof human embryos, but the experiments ended in a bust. The new report is the second time researchers in China revealed that they had a go at making genetically modified human embryos.

The controversial experiments are, in effect, feasibility studies of whether it’s possible to make super-people engineered to avoid genetic disorders or resist disease.

“It is foreseeable that a genetically modified human could be generated,” according to Yong Fan, a researcher at Guangzhou Medical University, who published the report.

Story via
MIT

His team collected more than 200 one-cell embryos and attempted to alter their DNA to install a gene that protects against HIV infection. The study, published two days ago in an obscure reproductive journal, was first spotted by reporters at Nature.

The scientists cautioned that they believe making actual genetically modified babies should be “strictly prohibited”—but perhaps only until the technology is perfected. “We believe that is necessary to keep developing and improving the technologies for precise genetic modification in humans,” Fan’s team said, since gene modification could “provide solutions for genetic diseases” and improve human health.

The Chinese scientists tried to make human embryos resistant to HIV by editing a gene called CCR5. It’s known that some people possess versions of this gene which makes them immune to the virus, which causes AIDS. The reason is they no longer make a protein that HIV needs to enter and hijack immune cells.

Doctors in Berlin demonstrated the effect after they gave a man sick from HIV a bone marrow transplant from a person with the protective gene mutation. The man—known since as the “Berlin patient”—was cured of HIV, too.

Using the gene-editing method called CRISPR, Fan and his team tried to change the DNA in the embryos over to the protective version of the CCR5 gene in order to show, in principle, that they could make HIV-proof people.

Almost exactly a year ago, in a world first, a separate group in Guangzhou said that it had altered embryos in an effort to repair the genetic defect that causes a blood disease beta thalassemia.

That set off an ethical debate, and last December the U.S. National Academy of Sciences, along with British and some Chinese scientific leaders, said any attempt to make a gene-edited baby would be “irresponsible,” a message that in many ways seemed directed at IVF doctors in China.

In February, U.S. officials went further, calling gene-editing a “weapon of mass destruction” and making a point of singling out the earlier Chinese research.

One day endowing people with protective genes could become a real possibility. It would be like a vaccine, except one that is installed in a person’s genome from birth. And there’s a long list of genes people might demand for their children in addition to HIV resistance. One DNA change, for instance, seems to completely prevent Alzheimer’s. Another generates people with twice the muscle mass.

But that’s a ways off, and Fan’s team said its experiments essentially flopped. They only managed to successfully edit a handful of embryos, and even these ended up as “mosaics,” or a mix of cells, some of which had the new gene, and some that didn’t.

 

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HIV defies attempt to edit virus out of human cells with CRISPR

Crispr

Vanquishing HIV just got that little bit harder. A promising technique to weaken the virus has in some cases made it stronger.

HIV’s ability to evolve resistance to antiretroviral drugs has become legendary. It had been thought that a new precision gene-editing tool called CRISPR would have more success, enabling the viral genome to be “cut” from all infected cells. Now it seems that hope may be in vain – at least for now.

Curing people with HIV has proved impossible so far. Several prominent reports of cures three years ago turned out to provide false hope, after the virus bounced back.

The problem begins with the fact that HIV integrates its genome into the host cell’s DNA. While antiretroviral drugs keep people free of active infection, this viral DNA hides out in parts of the body they can’t reach, ready to revive active infection if the drug treatment is stopped.

Story via New Scientist
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CRISPR cuts

Using CRISPR to cut up the HIV genome in all cells – including those where it’s hiding out – is one of several promising strategies to clear the infection.

But it has been hit with a serious setback. Research shows that the use of CRISPR to destroy the virus in white blood cells by messing up its DNA is a double-edged sword.

Chen Liang of McGill University AIDS Center in Montreal, Canada, and his team used CRISPR to cut up the viral DNA that had been incorporated into the host cell. The idea was that when the cell’s natural repair mechanisms patched up the broken genetic sequence it would introduce genetic “scar tissue” that would prevent the viral DNA from functioning.

Sometimes this did, indeed, happen – the gene alterations “killed” the virus. But to the surprise of the researchers, in other cases the scar tissue made the virus stronger – sometimes it was able to replicate faster, for example.

What’s more, because the patched up DNA looks different, the CRISPR cutting system couldn’t recognise and attack it again. HIV had become resistant to the gene-editing technique.

Double-edged sword

“On the one hand, CRISPR inhibits HIV, but on the other, it helps the virus to escape and survive,” says Liang. “The surprise is that the resistance mutations are not the products of error-prone viral DNA copying, but rather are created by the cell’s own repair machinery.”

But all is not yet lost.

“The bright side is that when you know what the problem is, you can come up with the means to overcome it,” says Liang. “Just as HIV is able to escape all antiretroviral drugs, understanding how HIV escapes only helps you discover better drugs or treatments.”

One possibility is to “carpet-bomb” HIV with CRISPR at many sites within its DNA instead of just the one targeted in the experiment. This, says, Liang, would make it much more difficult for the virus to evolve resistance.

HIV neutralised

Another potential ploy is to attack the virus with CRISPR-like techniques that rely on different DNA repair machinery, making it less likely that the repair process itself would help the virus become resistant to editing.

Another team reporting early success against HIV using CRISPR isn’t discouraged by the setback, echoing the possibility that the “carpet-bombing” solution could be the answer.

“The key could be using multiple viral sites for editing,” says Kamel Khalili of Temple University in Philadelphia, Pennsylvania. “This would reduce any chance for virus escape or the emergence of virus resistant to the initial treatment,” he says.

Earlier this year Khalili’s team showed that CRISPR neutralises HIV in cells that are latently as well as actively infected, suggesting that a cure could one day be possible.

Journal reference: Cell Reports, DOI: 10.1016/j.celrep.2016.03.042
 

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HIV cure now a step closer after scientists make gene editing breakthrough

Genome editing, or genome editing with engineered nucleases (GEEN) is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome of an organism using engineered nucleases, or "molecular scissors.

Genome editing, or genome editing with engineered nucleases (GEEN) is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome of an organism using engineered nucleases, or “molecular scissors.

American scientists have made huge strides towards finding a cure for HIV using pioneering ‘gene editing’ techniques.  After years of research, the team from Temple University in Pennsylvania used their technique to eliminate the virus fromhuman cells by ‘snipping’ it out.

Story via The Independent
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The successful experiments took place in the lab, but the team is confident the treatment could be trialled on humans within three years.

In a 2014 study, the researchers successfully managed to remove the HIV DNA from normal human cells.

This time around, they used the same technology to remove it from infected T-cells, which play a major role in the immune system, in a more accurate simulation of how the virus would be treated inside patients’ bodies.

During their studies, the team drew blood from people living with HIV. Their T-cells were cultured in the lab, and then treated with the Crispr/Cas9 gene editing system, in which a targeted protein uses enzymes to remove genetic sequences (in this case, HIV DNA) from cells.  Their results definitively proved it is possible to eliminate the virus and prevent it from re-infecting cells using this treatment.

Gene editing is an important field for medical researchers, but there are fears that the process could have negative effects beyond the boundaries of the cells, resulting in further health problems.

However, using highly-detailed genome sequencing to analyse the treated cells, the scientists found they continued to grow and function normally, and didn’t appear to be suffering from any side-effects.

“They demonstrate the effectiveness of our gene editing system in eliminating HIV from the DNA of T-cells and, by introducing mutations into the viral genome, permanently inactivating viral replication.”

Speaking to The Telegraph, Khalili said the study has “huge potential,” and added: “Based on the findings we should be entering into clincical trials within three years.”

A paper detailing their study has now been published in the high-profile Scientific Reports journal.

 

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