Helping HIV patients and the CCR5 gene

I’m sure you have heard of the virus HIV (Human immunodeficiency virus infection) also known as AIDS (acquired immune deficiency syndrome).

Thought to be first transferred to humans in the late 1920, this virus was most probably as a result of chimps carrying the Simian Immunodeficiency Virus (SIV), a virus closely related to HIV. For someone with HIV, the symptoms for the virus are very unclear. But here’s the problem, symptoms don’t really appear until HIV progresses and becomes AIDS. But it included flu-like symptoms such as, fever, chills and fatigue. This is very unfortunate for someone living with HIV because they wont know them selves what they have unless they get tested.

According to a government website, there are about 1.1 million people living with HIV right now!!! Another problem with that is that one is every 7 people dont even know about their infection. This seriously increases the chances that this person can spread the virus.

Now here is the scary part…there is no cure. Right now the only thing a patient can take is antiretroviral therapy (ART) which can dramatically slow the disease’s progress, prevent secondary infections and complications, and prolong life.

But going under this treatment is not so easy. Here are some of the devastating side effects

• Nausea and vomiting
• Diarrhea,
• Difficulty sleeping,
• Dry mouth,
• Headache,
• Rash,
• Dizziness,
• Fatigue, and
• Pain

Another problem with antiretroviral therapy is that it must be taken everyday or at least every single time it is prescribed by your doctor. It works by preventing the spread of the virus and so missing a day could lead to symptoms.

I think we can all agree that having HIV is terrible. But what if I told you there was an easier way.

Introducing…GENE EDITING!!!!!

Every single thing on our planet has genes and/ or genetic material. This is the blueprint or instructions for every single protein in our body. Now imagine we we could “change” the instructions for yourselves or give it new instructions! Many diseases are genetic, like Tay Sachs diseases, Huntington's diseases or ever sickle cell anemia.

Now on to HIV.

There is something really special about HIV that makes it unique. When the virus infects a human it targets CD4 cells. These cells are one of the most important parts of our immune system. And so our body has a really difficult time getting to the virus and eliminating it.

But using gene editing we are able to use this “power” it has against it. As soon as HIV enters the body it starts looking for these CD4 cells. These CD4 cells have a special receptor that gives them “permission” to insert its DNA into it. This is called the CCR5 gene.

This is exactly what they did at the Perelman School of Medicine.

CCR5 is a major co-receptor for human immunodeficiency virus(HIV). It is needed for the HIV virus to enter into the CD4 cell. For this experiment autologous CD4 T Cells were inserted into the patients body.

However these CD4 cells have been genetically modified. They were modified using zinc-finger nuclease (ZFN)

So zinc-finger nuclease fall under the category of Restriction Endonuclease.

A restriction endonuclease is an enzyme that cuts the DNA molecule at, or near to, a specific nucleotide sequence to produce discrete DNA fragments that can be separated by gel electrophoresis.

Okay so whats a “zinc-finger”? Well this is basically a protein that has a zinc ion. This ion then causes the protein to fold making it look almost like a finger. Now these zinc finger nucleases will only bind too one codon a.k.a 3 base bairs. So in order to take out a gene out have to make multiple connections of there zinc finger nucleases and then using two halves of a Fok1 enzyme, you make your cut!

Now using this gene editing technology, the proposal was to edit the genes, specifically (CCR5) of a CD4 cell in order stop it from producing the CCR5 receptor.

Why?

Well going back to HIV, this is a very important co-stimulatory molecule for HIV to infect CD4 cells. Now by removing it, the proposal was that the HIV virus could not longer inflect the CD4 cells and there for not proliferate.

In this study exactly 12 patient's were enrolled. All of the patients had cronic HIV infections. All of the patients were also actively receiving antiretroviral therpy.

This group was then split into two groups, six in each. One of the groups (six patients) underwent an interruption in their antiretroviral therapy. This was 4 week after receiving a dose of CD4 cells. They all each received a dose of about 10 billion CD4 cells in which 11 to 28% of these cells were genetically modified with ZFN.

After 252 days of recording symptoms and looking at the make-up of the blood, it was recorded that CCR5-modified autologous CD4 T-Cell infusions are safe if within the limits of this study.

There was one serouis outlier. One patient had to go to the hospital with fever, chills, joint pain and back pain within 24 hours of infusion.

However if we look at the results of the other patients there was a significant increase in the CD4 cell count. It went from an average of 448 per cubic millimeter to 1517 per cubic millimeter at week one. After that the number of CD4 cells continued to decline progressively to about 615 cells per cubic millimeter. During the whole study the number stayed above the baseline level of 256 cell per cubic meter. This showed that this therapy was relatively safe.

HIV has been among us but by leveraging new technologies we are able to find innovative ways that we can “cure” or “avoid symtoms”. New technologies can also be used in this situation. gene editing technologies like CRISPER are on the rise as popular ways to edit our genes.

Finally conclusions

Zinc-finger nucleases can be used to edit the genes of a CD4 T Cell. The gene CCR5 is a crucial receptor for HIV and by removing it from the CD4 cell we can achieve lower rates of HIV RNA in the blood.

Technologies like CRISPER and Prime Editing are on the rise as potential more accurate gene editing techniques. Hopefully we can see a future free of genetic diseases. Although there are many concerns with this technology, such as designer babies, it can be agreed upon that the potential is high for good and positive uses.

Thanks for reading! Feel free to check out my other articles on Medium and connect with me on Linkedin!

If you’d like to discuss any of the topics above, I’d love to get in touch with you! — Send me an email at sbmohammed03@gmail.com or message me on Linkedin!