The HIV virus has infected millions of people all around the world in the last century and many of them lost their lives as there wsere no appropriate drugs for this contagious disease. In addition to this, there were no plausible signs of finding a cure. Fortunately, in the last decades of this century scientists have come to some progress and managed to save many lives, but the cure was still not found.
On the horizon there is a new breakthrough in terms of this disease, namely scientists have succeeded to remove the HIV from the entire genome in laboratory mice. This happened for the first time by using a slow-acting drug and gene-editing.
This breakthrough was released in a publication today by presenting the two-pronged technique that could be the first universal cure in human beings. The human clinical trials are planned for the next summer.
Since this disease has occurred only two people have been completely cured, but they were two specific cases who suffered from terminal blood cancer as well and had to be submitted to a risky bone marrow transplant that destroyed both diseases.
Although the transplant technique was successful in these two patients for others it was fatal. This technique is applied only when the patient suffers from HIV and cancer.
The team worked on this project for five years lead by an HIV expert in Nebraska, Dr Gendelman and a gene-editing expert in Philadelphia, Dr Kamel Khalili. They managed to successfully remove the HIV from the entire genome of a third of their lab mice by using a slow-acting drug named as LASER ART and followed by CRISPR Cas9 gene-editing.
They were also surprised by the results that in the first instance they saw it they believed it is some kind of mistake. Here it is what Dr Howard E Gendelman, Director of the Center for Neurodegenerative Diseases at the University of Nebraska Medical Center, told DailyMail.com:
“We didn’t believe it!
We thought it was a fluke, a problem with the graphs; that the cells carrying HIV had died; that our assay system was wrong. It was only after we repeated it a couple of different times, that we accepted the results.”
Not only that they did not believe in their results, but also journals did not want to accept them and always rejected their publication of HIV cure.
Dr Gendelman stated the following:
“After we got it right, we submitted it for publication and it was rejected from many different journals. They had a hard time believing HIV could be cured.”
Dr Gendelman and Dr Kamel Khalili, of Temple University in Philadelphia prepared a comprehensive paper with additional 20 supplemental figures which is not common, but did it in order to prove that their results were not a fluke. This turned to be successful and the Nature Communications released their publication.
Dr Gendelman adds the following:
“There was a lot of frustration, self-introspection, denials, reaffirmation, and just laborious day by day activities to prove it”.
HIV is a virus that infects the genome, and cannot be easily detected as it hides till it appears at some point. Nowadays, the HIV is kept under control thanks to the use of effective drugs like ART, (the anti-retroviral therapy) that is so effective that suppresses the virus to such an extent that it becomes undetectable, and thus it cannot be transmitted to another person. ART is a soluble drug that dissolves into the blood and in that way acts against the virus preventing the occurrence of AIDS. Hence, people with HIV can have a long, healthy life without the virus turning into AIDS.
However, ART cannot reach the hidden reservoirs where HIV hides.
As a result of that, Dr Gendelman has created a new technique along with Benson Edagwa, PhD, Assistant Professor of Pharmacology at Nebraska, and named it as LASER (the long-acting slow-effective release) ART.
The improved drugs in LASER ART can reach the HIV in the hidden reservoirs as they are packaged inside with nanocrystals that the immune system recognizes them as foreign and thus carries it up to the reservoirs of HIV. Inside the reservoirs, the nanocrystals slowly dissolve, releasing ART into the most difficult spots thus leaving it to act for an extended period of time.
This technique would be of great help for the HIV patients as it is taken only once per year. Dr Gendelman and his colleagues have showed that this technique is better and gentler treatment than the other used drugs. This treatment is being released slowly with fewer ups and downs which is not the case when a person is on daily medication.
Before the invention of this technique, his colleague, Dr Khalili tried to use CRISPR to completely remove the HIV from the genome of mice, but without success. The main reason why it was not successful is that fact that HIV replicates too fast for CRISPR to do its work.
CRISPR could work well if there was only one target, or a few, but in the case of HIV it was impossible as there were too many targets and it was impossible to get each one of them.
Dr Khalili was persistent in finding the solution how CRISPR can be effective and he approached his colleague and friend Dr Gendelman to try to use LASER ART that will corner and control the HIV virus, so that CRISPR can do its job.
In the beginning the combination of both techniques did not go smoothly. But, after years of trial and errors, they have hit the jackpot. They used the LASER ART first, and then followed by CRISPR-Cas9 to remove the virus which was successful in a third of mice. These lab mice were engineered to produce human T cells susceptible to HIV infection. In the beginning they removed in two mice out of seven, then in three out of six, then in four out of 10.
The next step was to sequence the entire genome of the mice in order to entirely remove the virus. Moreover, the implementation of their technique did not cause any chromosomal side effects of the gene-editing or some other problems in the genome. During the procedure everything seemed to be going in good order.
Dr Khalili said: “We were pleasantly surprised to get at the other two thirds of mice who still had HIV.”
Dr Khalili and his team are going further in their research by exploring another CRISPR technique, targeting not just HIV but also the CCR5 gene, which in fact is a doorway to HIV. It was concluded that people who do not have CCR5, or have a mutation of it are immune to HIV.
This technique was successful in mice, and now scientists are testing it on macaque monkeys. If everything goes well, the human clinical trials should start in summer 2020.
Thanks to this technique the humans are near to finding the cure of HIV. Dr Gendelman maintains that this technique is “a proof of concept”. He adds: “it shows it’s possible that HIV could be cured.”
In the scientific world this is considered an amazing breakthrough but many scientists ask for a wider pool of animals, and then initiating human trials before the technique gets approved.
Their peer, Dr Paul Freemont, Co-Director of the Centre for Synthetic Biology and Innovation, Imperial College London, stated the following regarding this remarkable study, quote:
“This is an exciting study showing that it might be possible to use a chemical and genetic editing therapy in combination to eliminate HIV permanently from infected cells.”
“HIV is very clever in that it embeds its own genetic code into cells which when activated can make more virus and so methods to both kill active viruses and also eliminate HIV genetic code in infected cells are needed.
However the number of mice used in the study is small and further trials will be needed to confirm this initial but exciting proof-of-concept study.
However, it is still an open question as to whether such an approach would work in humans, particularly off-target effects.”