A potential HIV treatment raises troubling questions about gene technology, but do the benefits outweigh the risks?

A promising new development in HIV research reveals a potential new avenue for treatment in the future. The proposed technique would utilise the CRISPR/Cas9 gene editing method to remove sections of the virus’s genetic code, rendering it unviable and unable to replicate further. This technique has already shown to be successful under laboratory conditions in mice.

Copyright: <a href='https://www.123rf.com/profile_alila'>alila / 123RF Stock Photo</a>The technology, though, raises troubling questions especially since it is becoming easier and easier to use. Would-be amateur genetic engineers can even buy do-it-yourself kits for about $100.

The research, conducted at Temple University in the USA, was in three mouse models. One of these involved a “humanised” model, in which human immune cells were transplanted into mice. The implication of the removal of the HIV infection from human cells, despite being in a mouse model, is that the research would translate well into human trials.

The study shows that the technique reduced RNA expression of HIV by between 60 to 96 percent. This inhibits the ability of the virus to replicate. This is causing speculation that gene editing could be the long-awaited cure for HIV.

CRISPR/Cas9

CRISPR/Cas9 is a recently-developed gene editing technique that has rapidly become a commonly used tool of many laboratories. In a metaphorical sense the technique functions like biological scissors, capable of removing small sections of DNA to be replaced by others. In the context of the HIV treatment, researchers removed the part of the gene in the virus responsible for replication.

Originally discovered in the genomes of E.coli, the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 biological system functions as a defence mechanism in bacteria and archaea against invading viral DNA. The bacteria remove a section of the viral DNA, which they integrate into their own genome using one of the Cas enzymes. This allows for future recognition of the same viral strain, through storage of crRNA (single stranded CRISPR RNA) sections containing copied genetic sequences of the virus.

This biological defence mechanism has since been turned into a gene editing tool. In 2012 it was discovered that by altering the crRNA that guides the CRISPR/Cas9 complex to its intended target DNA, the complex can be specifically targeted to any section of DNA, providing the genetic sequence has been mapped.

The mechanisms by which DNA is cut and recombined are complex. Put simply, Cas9 forms the cut of a cut and paste system. This is by engineering the crRNA sequence to remove a specified section of DNA, but leaving a section of the genomic code that a specifically designed new section of DNA can attach to. The system can then incorporate a “paste” function.

This allows for a relatively easy to use gene editing technique, that can remove, for example, mutated regions of a genome and replace them with the correct sequence. Or potentially remove genes responsible for certain diseases. In the case of the HIV therapy, the process seems to be simplified to just removing a section of code allowing the virus to replicate within the host’s cells.

Kamel Khalili, director of Temple’s Center for Neurovirology, is surprised by the overwhelmingly positive outcome of the study, telling CBS News “Over our years of research, all of this was frankly a big surprise. This research, so far, has yielded all pleasant surprises, frankly. I never thought that this CRISPR system was going to be working out so beautifully with such efficiency and precision when it first came onto the scene,”

The controversy

CRISPR/Cas9 suffers the same controversy that gene editing has for years. If the technology to remove disease before a baby is born is present, is it unethical to not alter the genes and allow the baby to suffer during its life? This has been countered by some who believe this manner of thinking leads down a slippery slope: at what point do we draw the line between altering genes for a more comfortable life, and altering genes for more trivial reasons such as appearance.

This line of reasoning typically culminates in the “designer baby” theoretical scenario, in which, in a future where genetic manipulation becomes common, parents may design their children as they see fit. People with certain traits might gradually be phased out of existence as fewer and fewer people are born with these characteristics.

As the technology is currently not in a state where this kind of outcome is possible, any pondering of the problem is entirely theoretical. A person may object to genetic engineering on religious grounds. Others may wish to avoid the potential that genetic engineering of their children may be an enforced procedure, overriding freedom of choice. Many ponder who it is that will eventually decide what is lawful and what is not when it comes to altering our own bodies.

Biological weapons?

The technology to modify genes has become increasingly accessible (CRISPR/Cas9 is relatively simple compared to prior methods), to the point that in 2016, a kit allowing armchair scientists to render the E.coli bacteria resistant to streptomycin in their own home, was on sale for 100 GBP (approx 100 USD). This kind of unmonitored experimental approach is justifiably worrying, as the potential for any person to begin modifying bacterial samples is hazardous.

The technology to edit a genome could become commonplace, many worry. This would allow for both biological advancements and for weaponising current diseases. For example, making a more deadly strain of the flu using this technique would theoretically be relatively simple, with catastrophic consequences if ever unleashed on the public.

Despite the fallbacks and potential dangers of genetic engineering, it has already helped the world in many ways. Genetically engineered crops for example have far higher yields and are cheaper to produce, allowing for a potential boost for the fight against world hunger. Genetically modified cell lines and model organisms are used routinely to express human genes in experiments to more accurately test medications and therapies before trials in humans.

One school of thought is that if a potential treatment for a disease is available, is it morally wrong to deny it to people suffering from the condition? Those suffering from HIV are unlikely to refuse a treatment that could have the potential to cure them.

HIV and the failure of other treatments

According to UNAIDS, there were 36.7 million people living with HIV and AIDS at the end of 2015. Since the start of the epidemic, 78 million people have been infected.

Huge numbers of people currently access retroviral therapy: 18.2 million people according to UNAIDS. This involves consistent treatment across the course of the person’s life which in some countries will be hugely expensive. Due to expense or unavailability, just over half those currently living with HIV are not receiving this treatment.

Many other potential therapies have been trialled over the years, though there has been no medication or therapy put forward that can cure the disease. Screening, diagnosis and the antiviral therapy have improved by a vast amount over the years, to the point now that if diagnosed at a young age a person may have a similar life expectancy to a person without the disease.

Previous attempts at the creation of a vaccine have resulted in failure. A trial run by Merck on a vaccine showed no signs of increased immunity to the disease following vaccination. Alarmingly the vaccine might actually have increased the rate of infection in those who already possessed some immunity to the adenovirus vector used in the vaccine.

The media is eternally on the lookout for the next promising “HIV cure” story. On one occasion, the so-called “Berlin patient” was genuinely cured of HIV, with only genetic remains of the virus left in his system that cannot replicate. This case is however unique, and not reproducible, as an assortment of chemotherapy, radiation therapy, antiretroviral drugs and bone marrow transplants were used. The case baffled the scientific community.

Other cases such as the “Mississippi baby” suggested that an extensive course of antiretroviral drugs during the first 30 days following birth could rid a child of the disease. This was later proven to be false as a month later it was revealed the virus was still present in the baby’s blood and actively replicating.

Curing rather than symptom management

Jeremy Luban, MD, the David J. Freelander Professor of AIDS Research and professor of molecular medicine says “HIV acts essentially as a bad gene, one that we want to get rid of.” Luban adds “It is a permanent member of an infected person’s genome, a permanent genetic element of your cells. CRISPR offers the possibility of removing it.”

Gene editing may be the future breakthrough that HIV research desperately needs, shifting the focus from symptom management to finally curing the condition.