With millions of people infected with the HIV virus world-wide, a cure has yet to be found. The reason why vaccines and drugs are so hard to develop for this virus relates to both mutation and latency of the virus.
When humans make copies of our DNA during reproduction, it’s reproduced with very high fidelity, where there’s one mistake made for every billion events. However, the HIV genome isn’t made from DNA, it’s made from RNA. And the enzyme that converts the RNA to DNA and then inserts it into a cell makes between one and 10 mistakes every time it copies itself.
So, when people have an active HIV infection, where they have millions of viruses for every milliliter of blood in their body, none of those viruses are the same. They are all different and they all have different changes in them.
What commonly happens with current vaccines and drugs is they work against, or kill, the original virus, but there are mutants that will be resistant and grow to repopulate the person.
Latency is also an issue. “And what happens here is when HIV infects someone, it makes a copy of its DNA and inserts into the white blood cells,” says Dr. Martin Schiller, Executive Director of the Nevada Institute of Personalized Medicine at the Univ. of Nevada, Las Vegas. ”And it puts its DNA into the white blood cell DNA so it becomes part of it.”
For example, if there is a drug that prevents the virus from being made, those cells could be stopped from making virus, but the blueprint to make the virus is still left in those cells forever. There is no known way to get rid of the virus. And as soon as drug regimens are stopped, the virus will come back and start reproducing from the blueprint.
In essence, you can’t cure HIV at the moment because it becomes part of a person.
Yet, this sad reality may be changed in the near future thanks to researchers with the Nevada Institute of Personalized Medicine at the Univ. of Nevada, Las Vegas, who have engineered a new protein believed to be a future HIV cure that tackles both issues noted above.
The protein, called HT-TALENs (short for HIV-targeted transcription activator-like effector nucleases), addresses both mutations and latency, and was developed by altering a commonly used plant pathogen protein. It uses a newly developed gene-editing technique to rid the body’s cells of HIV before it has a chance to multiply and possibly develop into AIDS.
“We took a large number of viruses and we got the sequencing, the equivalent of a computer code,” says Schiller. “And then we lined them all up and identified places in the virus that, even though it’s mutating, there are a few places that don’t change, because they are absolutely needed for the virus to reproduce.”
Once the team found these sections, they engineered the HT-TALENs protein that binds to that sequence and cut the HIV DNA, but not any of the human DNA. As a result, when that cut gets fixed, and it leaves a scar, it’s not exactly the same. This means the virus can’t come back and make the cells that have HIV DNA, and they aren’t capable of making the virus anymore.
And while existing drugs stop the virus from reproducing, they don’t rid the body of the virus DNA. “This protein is getting after the root cause of the disease,” says Schiller. “We are going after the actual DNA copy, and hopefully stopping virus replication in its tracks.”
Results and the future
So far the researchers have only produced results in Petri dishes. But what they have been able to show thus far is when they introduce their protein into cells in a Petri dish that are infected with live HIV, the HT-TALENs damage the HIV DNA and stop viral production.
“In our studies thus far, 60% of the cells making the protein damage the viral DNA,” says Schiller. “And the protein is killing the HIV and preventing it from making new viruses.”
“With our efficiency of damaging at 60%, we have some new developments where we think we can get that number much higher,” says Schiller. “And we have reason to believe this shouldn’t be difficult.”
The team has already made some new mutant forms of HT-TALENs that Schiller claims should have higher efficiency. “Actually we are starting testing of these new mutants next week,” says Schiller. “And what we are doing is moving the protein into a cold virus, so that when this virus is delivered to a person infected with HIV, they might get a cold, but on top of that they are going to get these proteins and they are going to start removing the HIV copies from the cells and the blood.” And this will be the team’s delivery system of the protein.
The team is currently awaiting patent approval and have started on the next phase of testing through a partnership with Brigham Young Univ.
“These things take a long time,” says Schiller. “And we have to go through testing in mice and then human trials, which is a long process, but we are on the right path.”
An actual time frame for the market use of the protein? Schiller believes if all goes well the best-case scenario is seven years, but it is likely to take longer.
The protein treatment’s success would be a boon emotionally and financially for patients undergoing current HIV drug regimens, which can top $15,000 a year.
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