When HIV-1 first emerged in the 20th century, researchers thought it was a new virus, but they have since figured out it is an ancient organism. In fact, a research published in the journal, PLOS Pathogens, is suggesting that it could be millions of years old. This might explain the elusive nature of the virus and its ability to adapt and overcome many of the assaults researchers have thrown at it. With more than 34 million people infected with the virus, it is still a condition that affects a large number of people around the world. Researchers at the Stanford University School of Medicine and the University of Texas at Austin are engineering key cells of the immune system to give the body the ability to withstand an HIV infection.
The virus’ ability to mutate at such a fast rate makes it difficult to destroy with just one type of medication. Currently, patients use what is known as Highly Active AntiRetroviral Therapy (HAART) consisting of six antiretroviral agents: Nucleoside reverse transcriptase inhibitors (NRTIs), Nonnucleoside reverse transcriptase inhibitors (NNRTIs), Protease inhibitors (PIs), Integrase inhibitors (IIs), Fusion inhibitors (FIs) and Chemokine receptor antagonists (CRAs). By targeting a different step in the lifecycle of the virus it is possible to slow down or stop the progression of the disease with a combination of these medications.
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"HIV is a great shape shifter. It can come up with new solutions, so a single drug does not work very well. That's why HIV patients are given multiple drugs at once." said Sara Sawyer, an assistant professor of molecular genetics and microbiology at the University of Texas at Austin and co-author of the study.
The researchers used genome editing by cutting and pasting a series of HIV-resistant genes into T cells. They then made the receptor gene inactive and inserted more anti-HIV genes, which blocked the virus from entering the cells. This prevented the virus from destroying the immune system.
“We inactivated one of the receptors that HIV uses to gain entry and added new genes to protect against HIV, so we have multiple layers of protection — what we call stacking. We can use this strategy to make cells that are resistant to both major types of HIV,” said Matthew Porteus, MD, an associate professor of pediatrics at Stanford and a pediatric hematologist/oncologist at Lucile Packard Children’s Hospital.
Gene manipulation is seen as the next frontier in medicine and the optimism researchesr have in this field is warranted because it offers achievable goals for many of the diseases plaguing mankind. In the case of HIV, the virus enters T cells by attaching itself to two surface proteins known as CCR5 and CXCR4. What the researchers have done is to mimic the naturally resistant version of these genes that occur in some individuals and change the proteins. They achieved this by creating a break in the DNA sequence and edited the gene by pasting three genes they know have the ability to resist HIV. This method allows the body to resist entry of the virus from the CCR5 and CXCR4 receptors creating multiple layers of protection.
The goal is to eventually stop using drugs and make gene therapy the weapon of choice in treating conditions such as AIDS. The research is only in the laboratory stage and dates for clinical trials could be three to five years away.
Edited by Brooke Neuman