Saturday, March 14, 2015

CRISPR/Cas9 System May Provide a Cure for HIV

     What do you think of when you think about human immunodeficiency virus, or HIV? For the majority of people, it is a taboo infection with no survivors and a huge social stigma. Since its discovery in 1981, people have been suffering physically and emotionally from the effects of this virus. In my opinion, it is incredibly difficult to accept that in the world, there are now upwards of 35 million human beings living with and suffering from this disease to which there is no known cure. 3.2 million of these people are only children- under the age of 15, and most of them live in third-world countries with little access to healthcare. It is about time for a viable long-term solution. According to experimental results accepted as of January 2015, there may be hope for a permanent cure for HIV.


     The HIV virus is very smart. It works by essentially hijacking a healthy cell, forcing the cell to make copies of the viral DNA, and then integrating these copies into the cell’s genes. Current drugs only interfere with HIV at certain steps: by slowing its replicatory process or stopping it from incorporating into the cell’s DNA. However, these drugs do not remove the existing viruses that are hidden in the DNA, so HIV can remain dormant for years and then suddenly activate. Also, patients might be on a cocktail of many different drugs that they need daily for their entire lives to combat the spread of HIV within their bodies, which costs a lot of money and time. These drugs can be very toxic to the human body, and can only hold off the infection for so long until AIDS develops. People can survive for years while on these drugs, but it is not a long-term solution; the virus will eventually take over.

http://www.genome-engineering.org/crispr/
     But what if there was a way to destroy the virus from within the DNA, including the hidden and dormant copies that are unreachable by the standard therapy? This is where CRISPR comes in. CRISPR (clustered regularly interspaced short palindromic repeats) is a molecular defense system originally used by bacteria and archaea. Scientists are beginning to use it as a way to edit DNA without damaging the human genes. Basically, CRISPR and CRISPR-associated genes (Cas9) work by using guide RNAs to make cuts in DNA, called DSBs (double stranded breaks). At the Salk Institute, scientists have engineered these guide RNAs to bind to and cut specific sections of the DNA of HIV. Once these were inserted into a cell infected with the HIV virus, it was found that CRISPR effectively cut the HIV, destroyed its genes, and thus inactivated the virus. This method was able to remove HIV from 72% of cells tested. It even inactivated HIV that was dormant and hidden in the genome of the cell, and the full-length, active version of HIV as opposed to a shorter, inactive version.
     The use of CRISPR in this manner is absolutely groundbreaking. Instead of stopping the amplification of HIV after  it has already manifested itself within the genome, this method cuts it off right at the beginning of its life cycle (no pun intended). CRISPR is able to provide long-term adaptive defense against future viral infections. In fact, when CRISPR was inserted into cells before infection, it prevented the uptake of HIV, killing the virus by chopping it up before it could even start replicating. To me, that sounds like a vaccine for HIV.
     To summarize, CRISPR could be able to prevent HIV, treat people who already have HIV, and even remove all the dormant copies of HIV in patients with a more advanced infection. But HIV is not the only virus that CRISPR can be engineered to work against! The CRISPR system and its proven success in this experiment  opens doors for the use of CRISPR against unlimited types of viruses and  diseases that were previously thought to be incurable. However, there are many obstacles in the future of CRISPR. How could we make this therapy a realistic option for those living in lower-income countries? And there is always the possibility that this therapy could fail in trial. It may take some time, debate, and a lot of advocacy before the therapeutic use of the CRISPR system becomes a reality for everyone who has HIV, but I am hopeful that soon we will be living in a world where HIV/AIDS is no longer a fatal disease, but one you could simply get a vaccination for.

References:

"HIV/AIDS 101" AIDS.gov. 11/13/2014 2014.Web. <https://www.aids.gov/hiv-aids-basics/hiv-aids-101/global-statistics/index.html>.

Liao, Hsin-Kai, et al. "Use of the CRISPR/Cas9 System as an Intracellular Defense Against HIV-1 Infection in Human Cells." Nature Communications (2015) Web.
<http://www.nature.com/ncomms/2015/150310/ncomms7413/full/ncomms7413.html>.

Salk Institute for Biological Studies. "Cellular scissors chop up HIV virus."

ScienceDaily. ScienceDaily, 10 March 2015.
<www.sciencedaily.com/releases/2015/03/150310073841.htm>.

8 comments:

  1. The CRISPR-Cas system is absolutely groundbreaking as a means to introduce site-directed deletions in large genomes. It is my understanding that the technology today is at a point where it is not yet possible to target specific bases within an exon, but there isn't any reason that I know of to think that within a few years we won't be able to neatly trim a viral sequence out of a host. In the case of HIV, however, I am wondering how the CRISPR-Cas system will be directed to those cells that are acting as reservoirs for HIV DNA. Even if we knew exactly which types of cells were acting as pools for the foreign genetic material, there is still the question of how to direct CRISPR-Cas complexes to those cells.

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    1. When CRISPR/Cas9 was applied to cells that did not have HIV DNA in it yet, it was proven that it could prevent the embedding of the HIV genes by destroying them before they could replicate. Maybe I'm wrong, but I don't see why there would be a need for directing the system because it could just be applied to all types of cells. Rereading the article, there were issues with HIV evolving to "escape" CRISPR, so you are right. More research is needed before they can put together more RNA sequences to neatly trim out more areas of viral DNA.

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  2. If this CRISPR-Cas is being used on HIV, have they used this method of destroying viruses on less complex, and slower to mutate viruses, i.e. HSVI? I feel that even though HIV is more popular in the press, showing this system is effective for other viruses is necessary as well. This is groundbreaking research, but there needs to be more proof. Where did they "chop" up HIV in a petri dish or in a living organism, because it make a difference on how effective it can be within a human body

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  3. You make a really good point about less complex viruses- I don't know why they picked HIV. However, I don't see why it wouldn't work on other viruses too. Also, in the paper that I read, the research team did insert the CRISPR system into human cells, and it worked. There is still research being done on how this will work in an actual human patient.

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  4. I heard about the power of CRISPR last semester, but it's amazing to think that (among the other things it can do) it can also be a cure for HIV. Because HIV mutates so often, I wasn't sure if a single treatment would work against most cases of it. Would CRISPR realistically be able to be used to prevent infection? Even besides the cost, it seems that this system would have to be integrated into the genome. Nonetheless, CRISPR does show great promise for being able to cure HIV, and hopefully there is some way to lower the cost enough to make it more accessible.

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  5. CRISPR seems like a very hopeful and effective method. I hope that they keep up with trials, testing this method, because with its ability to possibly wipe out HIV it would be amazing to see how many lives it could save. Additionally I also hope that there is a way to allow for this treatment in places of lower income so that it is available for all who needs.

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  6. To think that only a few decades ago HIV was killing millions of people, and now we are on the right path to have some type of cure for it is incredible to me. CRISPR seems really promising and I hope new experiments adds to the findings so far.

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