HIV: Cure in the near distance?

22. September 2014
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After three decades of symptom-based treatment, research efforts have now for the first time succeeded in completely liberating infected cells from HIV. Should this approach be transferred from cell culture to patients, curing HIV-infected people might be something within reach in the perceivable future.

It’s already about 30 years ago since HIV was discovered – yet in spite of that AIDS still presents one of the major health problems worldwide, having more than 35.3 million sufferers. Populations mainly affected are those living in sub-Saharan Africa. Nevertheless there are in Western countries as well people infected with HIV. Although those affected in western countries who initiate early treatment have a good chance of a long life, curing the disease has not yet been achieved, because HIV is tricky: It can hide in the genome of its host for a long time and thus evade drug therapies and attacks from the immune system.

Virus hides a long time

When one imagines the HIV particle, one thinks of a spherical structure with many small receptors on the surface. This is also entirely correct, but does not reflect the entire life cycle of the virus, because for a long period the pathogen is exclusively composed of DNA which unobtrusively places itself in the genome of the host. Even if no HIV particles are detectable in the body, scientists expect that there are millions of cells carrying copies of the viral DNA in them. Therefore, only the symptoms of the infection have been able to be treated up until now, but not its cause.

Molecular precision scissors

This situation could possibly change because scientists have now managed to cut the virus out from the genetic material of human cells with precision. For their experiments they used a culture of myeloid cells, because the neurons are considered a popular reservoir for HIV. In order to cut the viral DNA from the genome of the cells, the researchers employed a molecular-level precision tool called CRISPR Cas9. This technique, first publicised in 2012, is based on a protein used by bacteria to defend themselves against attacks by foreign organisms. This adaptive bacterial defence system has now had its functions converted by scientists into a microbiological precision scalpel for use in eukaryotic cells.

Tracking down the needle in the haystack with precision

Cas9 functions like a pair of molecular scissors, cutting out the DNA of HIV selectively from human chromosomes and thus preventing more virions from being formed. The action of Cas9 is described by the scientists as “highly specific and efficient”. “We have been able to transform the cells carrying the virus into completely virus-free cells”, says study leader Prof. Dr. Kamel Kihalili from Temple University in Philadelphia, USA. The challenge here is first of all that we need to be certain that Cas9 finds all the viral DNA – and that, when searching among about three billion base pairs of the human genome, isn’t so easy, considering that the HIV virion has only 9,181 base pairs. If Cas9 overlooks any viral DNA, it may have just as serious consequences as would cutting in places that do not contain any viral DNA, which could result in cancer or other such negative consequences.

Guide RNA shows Cas9 the way

In order to minimise these risks, the scientists have provided the system, known as CRISPR (Clustered Regularly Spaced Inter Short Palindromic Repeats) -Cas9 system, with a guide RNA (gRNA). This binds to specific DNA segments that occur exclusively in the viral DNA and thus leads the molecular scissors safely to their destination.

In wanting to have certainty, the scientists studied the genome of the neuron cells to determine whether Cas9 had perhaps also cut other sites without viral DNA. However they were not able to prove that any single enzyme miscut had occurred. In cell culture, this HIV healing therefore worked flawlessly and even brought a very useful secondary effect with it: healthy cells that contained the Cas9/gRNA complex were in laboratory tests immune to HIV infection. “The system could therefore also find application as a vaccine against HIV”, says Kihalili.

The path from cell culture in the laboratory to application in patients is still admittedly a long one. This is also understood by the scientists: “The system has potential, but it is a great challenge to get this molecular precision tool into every cell of the body”, says Kihalili. The HIV genome moreover is also susceptible to mutations. Therefore, the gRNA first needs to be defined anew for each patient. “We hope that the system works just as well in the human body as in cell culture”. If so, curing HIV, after more than three decades of study and work on it, would for the first time be within reach.

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1 comment:

DOCTOR Abadi Leul Welderufael
DOCTOR Abadi Leul Welderufael

Hopefully this is it!!!!

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