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Eliminating Hiv – A New Hope

The discovery of combination anti-retroviral therapies (ART) in 1996 was instrumental in changing the status of HIV-AIDS from ‘feared death sentence’ to a ‘chronic manageable disease’.
The treatments have been revolutionary and are a testament to the pursuit of scientific discovery. However, the search for a cure continues. The ART medicines are able to contain the development of AIDS to a large extent, however, there are still many individuals infected with HIV in whom the drugs do not work. Cutting-edge research is being conducted along many promising avenues including new pharmaceuticals, antibodies, vaccines and cell therapy. A few years ago a seismic shift occurred in our ability to modify DNA and it is impacting HIV research and the way we think about the possibility of a cure.
A new genome editing technology took the world of DNA biology by storm since it was first developed from the bacterial immune system in 2012, and shown to work in human cells in 2013. The user-friendly tool, known as CRISPR is very simply a protein system from which works like a DNA scissor. This technology has turned ...
... gene editing from complex and tedious to simple and fast. Most importantly, unlike previous methods, CRISPR is programmable and specific, which means it can be used to edit DNA for many different purposes. The applications of the technology are innumerable and extend from making better yogurt and beer, to curing congenital illnesses.
Particularly for HIV, the approach using gene editing has been two-pronged.
To design a molecular scissor that will precisely identify a unique stretch of DNA in the HIV genome and snip it, such that the virus can no longer replicate. The uniqueness of the genetic code that the scissor identifies can mean that there is no snipping of host (human) DNA and that means the therapy can be safe. Although possible, early results indicated that the HIV virus is able to very quickly adapt to the DNA cutting. The adaptability of the virus, proving once more how clever and slippery it can be. However, leading researchers Atze Das and Chen Liang, both believe that the problem is surmountable.
The second approach is to change the genes of the patient enable them to overcome HIV. A small percentage of individuals who have been repeatedly exposed to human immunodeficiency virus type 1 (HIV-1) over long periods of time, remain free of any detectable sign of infection. Genetic studies on these ‘resistant’ people found that they possessed a mutated form of a gene called CCR5. Scientists have used an older gene editing technology called Zinc Finger Nucleases (ZFN), to harvest immune cells from patients and introduce a mutated CCR5 to mimic the DNA of the ‘resistors’. Once the immune cells have been edited, they are reintroduced into the patient to fight the infection. In a clinical trial conducted by Paula Cannon and group at the University of Southern California, 6 of the 12 participants then stopped their antiretroviral drug therapy. After treatment, all 12 had elevated levels of T cells in their blood, suggesting that the virus was less capable of destroying them.
Using CRISPR to achieve similar editing as the ZFN approach, promises a faster more efficient way forward.
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Along with all these marvelous scientific breakthroughs, riding the wave of gene editing also brings ethical questions. In February 2016, scientists in the UK received approval to edit genes in human embryos. At this time, the approval is highly regulated and strictly limited to the purpose of studying development. The embryos will be ones donated by IVF patients who have undergone treatment. The edited embryos can only be in culture and not used for implantation. It remains illegal to alter the genomes of embryos used to conceive a child in the United Kingdom.
However, the slope can be slippery. While the advances promise great hope for unmet medical needs, they also demand a closer look at when it comes to editing inheritable traits how far is too far. The widespread use of CRISPR and related technologies is helping scientists leap through phases of discovery like never before. It has also brought ethical questions to the surface. If in the near future we could ‘design’ babies… should we?
Dr. Radha Desai is a neuroscientist and works in London. Her research is focused on mitochondrial and bioenergetics, with the specific aim of finding cures.
CHQ strives to build a community of writers who are driven by the sheer joy of spreading the word. By supplying to an ever-increasing demand for relevant content across the globe, CHQ provides a data-driven reality check to stir thoughts around the need for healthcare innovation. More than finding answers, we are invested in asking the right questions.
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