BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: HIV cure

CRISPR/Cas9: Is it really the cure?

There are many benefits to the CRISPR/Cas9 defense system. But, do the pros outweigh the cons?

CRISPR is a molecule that can be programmed to target a specific sequence in a genome. It guides an enzyme, such as Cas9, to chop the code like scissors. There have been many studies and tests done using the defense. The most important advantages of CRISPR/Cas9 over other genome editing systems are its simplicity and efficiency. Since it can be applied directly in the embryo, CRISPR/Cas9 reduces the time required to change certain genes compared to other systems.

However, many attempts to use this mechanism have failed. Using the mechanism is not as easy as it sounds. A Cas9 repair is not always precise. On ZMEScience, one HIV patient tried the process. But, the HIV cells were only made stronger. Researchers equipped T-cells to hurt the virus with the enzyme Cas9. T cells are a type of lymphocyte that play a central role in cell-mediated immunity. T cells equipped with Cas9 were seen to successfully hurt the HIV genome, and make it unable to properly reproduce. This project led by Chen Liang from McGill University in Montreal, Canada seemed to work fine. But, the team noticed that two weeks later T cells were producing copies of virus particles that had escaped the CRISPR attack. The area around Cas9 only developed more mutations, aka it made the HIV stronger. It is also impossible to direct the Cas9 exactly where one wants it to go. So in essence, it is a risky gamble.

Although there are hopes for this technique to be more refined and successful in the future, for now, its uses are limited.

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HIV Adapts to CRISPR-Cas9 Treatment

There has been an abundance of research using CRISPR/Cas9 gene editing to search for a cure for HIV. The HIV virus enters immune cells and uses the host cell’s method of replication to replicate the viral genome. With CRISPR/Cas9, specific mutations can be introduced in order to make it more challenging for the HIV virus to enter Helper T-Cells. Guided by specific strands of RNA, the Cas9 enzyme can cut a particular piece of the viral genome out, rendering it useless.

When a team of researchers at McGill University attempted to use the CRISPR method to disable the HIV viral genome, they found a major roadblock. Two weeks after the CRISPR/Cas9 treatment, the host cells appeared to be creating copies of the virus. This may be attributed to an error in the enzymes that copy the viral DNA, causing a change in the genome, and a mutation that allows it to evade the CRISPR treatment. However, the McGill researchers believe that this mutation was a result of the CRISPR treatment itself.

After DNA is cut by the Cas9 enzyme, the host cell usually attempts to repair the damage. Occasionally, this results in the addition or deletion of a few nitrogenous bases. While these changes usually result in the inactivation of the cut gene, sometimes they don’t. The active cut DNA is no longer recognized by the machinery used to prevent HIV infection of the cell, and the mutated viral genome is resistant to the usual methods of disablement.

More researchers at the University of Amsterdam had similar results in their research. While it is not that surprising that HIV can overcome the CRISPR/Cas9 gene editing at some point, the leader of the research (Atze Das) said “What is surprising is the speed- how fast it goes”.

If CRISPR was used at the same time as HIV-attacking drugs (inhibitors of protease, reverse transcriptase, and integrase), perhaps the mutations would be less  detrimental. This roadblock does not mean that a CRISPR cure for HIV is impossible, but it does make it far more challenging to overcome.

Possible HIV Remedy?

There wide array of deadly diseases that affect millions of people worldwide. Do you ever wonder if there could be a cure for just one? A team of researchers led by Dr. Caroline Goujon and Professor Mike Malim at the Department of Infectious Diseases in King’s College London has recognized a new gene that may have the ability to prevent HIV (Human immunodeficiency virus), a virus that slowly replicates and eventually causes AIDS. AIDS is a human condition that causes continuous failure of the immune system that could potentially lead to life-threatening infections and cancers. The research team has concluded that the human MX2 gene could play a major role in the path to finding an official cure for the deadly virus.

The MX2 gene is the Interferon-induced GTP-binding protein MX2. The protein encoded in this gene has nuclear and cytoplasmic forms. Researches have concluded that this protein could “lead to the development of new, less toxic treatments where the body’s own natural defense system is mobilized against the virus.” The scientists began the experiment by presenting the virus to human cells where the HIV virus had an encounter with two different cell lines and observing effects. After an intense study of the experiment, they detected in one cell line the MX2 gene was “switched on” and in the other cell line the gene was “silenced”. In the cell where the MX2 was switched off the virus duplicated, but in the cells were the gene was switched on no new viruses were produced or continued. In this way, the gene tested positive for its ability to fight off the virus.

The recent finding by the researchers brings way for other researches and scientist to continue to advance their knowledge about the virus. The goal would be to allow the 34 million people worldwide who are infected with HIV to lead a life free of the virus.hiv

 

Can HIV finally be cured?

While the answer to this question is very broad, there is hope that the number of people living with HIV throughout the world will significantly decrease in the near future due to a toddler who was cured of the virus.

About 1000 infants are born with HIV every day, that’s about 330,000 children each year. While most of the infections are in the developing world, there is still a vast number of people living with HIV in first world countries. An example is the Mississippi mother who had no idea she had HIV until a few days before she gave birth to her baby. Once the doctors learned she was infected with the virus, they took precautionary measures to ensure they could prevent the transfer of HIV during birth, a very common way of HIV transmission along with breast feeding. Once the baby was born Dr. Hannah Gay administer three drugs to the baby within thirty hours of birth. Typically, babies born from mothers with HIV are given two drugs as a prophylactic measure, however Dr. Gay said “her standard is to use a three drug regimen to treat an infection. She did this on the infant without waiting for HIV test results” (CNN.com)

Gay believes that the timing of the drug treatment was extremely crucial, and is key to effectively treating HIV in children/newborns. Currently, researchers are trying to see if this “cure” is an anomaly for a short period of time, or if the cure is permanent. In addition, physicians and scientists are optimistic, hoping that this cure will prevent many children from living with HIV throughout the world. Although the antiviral medications are very costly, doctors believe that it is not a stretch to offer these medications in third world countries and are hoping to soon make these medications available to many clinics throughout the world, assuming the “cure” was a success.

Read more at: http://www.cnn.com/2013/03/05/health/hiv-cure-global-hope/index.html?hpt=he_t3

Cute Baby
Photo By: Christopher Lance
http://www.flickr.com/photos/ninedragons/4822437519/

 

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