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The field of research concerning HIV and AIDS has been in constant drive to bring forth better treatments for the patients suffering. While prior studies have found the efficacy of some treatment methods, none of them did involved directly the HIV-1 DNA and the genetic unit involved in it.
A new study (R) conducted by the researchers from the Temple University Health System has successfully eliminated the replication competent HIV-1 DNA, the primary virus which is behind the induction of AIDS, from the genome of some of the living animals. The study does open up better possibilities of finding and developing effective treatment options for the condition.
This has been a collaborative study between the researchers from the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center. The reports were published on July 02nd, 2019 in Nature Communications which a further drive towards developing effective treatment options for HIV and AIDS.
Kamel Khalili, PhD, Laura H. Carnell Professor and Chair of the Department of Neuroscience, Director of the Center for Neurovirology, and Director of the Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine at Temple University further stated saying that the main subjective behind their study that the consecutive treatments to suppress the HIV replication followed by the gene editing therapy can actually be helpful in eliminating the HIV virus from the cells as well as the affected organs.
The study was directed under the senior investigators, Kamel Khalili and Howard Gendelman, MD, Margaret R. Larson Professor of Infectious Diseases and Internal Medicine, Chair of the Department of Pharmacology and Experimental Neuroscience and Director of the Center for Neurodegenerative Diseases at UNMC.
Dr Gendelman did clarified stating that none of this would have been possible with the dedicated team of immunologists, virologists, pharmaceutical experts, molecular biologists and the pharmacologists that they have in the backend supporting them through the process. Pooling the knowledge and the expertise was the only way everything in this was made possible further.
With the researches and the current scenario, it has been found that the current HIV treatment does solely focus on the antiretroviral therapy which does suppress the overall prospect of the HIV replication but doesn’t help in eliminating the virus from the body.
The researchers suggested saying that the antiretroviral therapy isn’t the cure for HIV but a mere way to keep the condition from getting worse. It needs to be administered on a regular basis, the stopping of which definitely does have impacts in making the HIV to rebound. What this does is again renew and start with the replication process all the more, thus fueling the induction of AIDS once again.
The rebound of HIV has been linked with the ability of the virus to end up integrating its DNA directly into the genome of the host in the immune cells specifically. There it remains in the dormant state and also beyond the reach of the antiretroviral drugs.
In prior case studies with this, Dr Khalili along with his team of researchers leveraged the use of CRISPR-Cas9 technology to help develop a gene editing and the gene therapy delivery system to help in removing the complete HIV DNA from the genomes directly.
Furthermore, in the rats and mice, they found that the procedure of gene editing was successful enough in excising large fragments of the HIV DNA from the infected cells, which further impacted the viral gene expression. Much like the antiretroviral therapy, the gene editing process wasn’t that effective in completely getting rid of the HIV virus on its own.
With the knowledge from the prior study, Dr Khalili along with his other researchers combined the prior gene editing system along with a new developed therapeutic strategy long-acting slow-effective release (LASER) ART. The LASER ART was the result of the work put into by Dr. Gendelman and Benson Edagwa, PhD, Assistant Professor of Pharmacology at UNMC.
LASER ART helps targets the viral sanctuaries and also helps in maintaining the HIV replication process at low levels for an extended period of time. What this does is further help in reducing the frequency of the administration of the ART. These long lasting medications were developed with effective changes made to the pharmacological changes in the possible chemical structure of the antiretroviral drugs.
These new developed drug was then packed into the nanocrystals that effective distributes itself into the HIV affected tissues where the virus possibly stays dormant for extended periods of time. After the drug targets the tissues, the nanocrystals which are stored in the tissues for weeks then start to slowly release the drug into the system to further eliminate the spread.
In order to test the efficacy of their procedure, the researchers did use mice which were engineered the human T cells which were immune to the HIV infection. This induced the prospect of the long term viral infection following the ART-induced latency.
Once the infection was induced successful, the mice were tested upon with the LASER ART process followed by the CRISPR-Cas9 to test out whether or not the same was effective enough to treat the condition effectively.
At the end of the conducted tests, the mice were checked for any kind of viral load and found that the same was effective in the complete elimination of the HIV DNA in 1/3rd of the HIV infected mice which were tested out in the study.
Concluding everything, Dr Khalili suggested saying that it does takes the combined process of the CRISPR-Cas9 along with the viral suppression procedure with the LASER ART to effectively get rid of the complete HIV infection altogether. With the basic research completed in the non-clinical trials in elimination of the HIV-1 DNA from the genome, the next step is to test out the same on the primates and the other non-primates and then possibly even clinical trials to check for their effectiveness.
