Dr Abdul Razak Shaikh
SCIENTISTS in the US have been able to completely remove HIV from a living animal using gene editing. The research is a major milestone, giving hope that a cure could be on the horizon. Ever since the world woke to the unfolding the tragedy of the AIDS epidemic, we have been desperate to solve the problem of removing all traces of the human immunodeficiency virus (HIV) from a human body. AIDS is still a major global health concern. It is caused by HIV infection and induces immune destruction there are two different types of HIV, HIV-1, and HIV-2. They both have many similarities and both can lead to AIDS. Compared to HIV-1, HIV-2 has lower transmissibility and is less pathogenic. HIV-1 is recognized, despite the fact that great efforts have been made in the prevention and therapy of HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. Highly active antiretroviral therapy (HAART) can suppress virus replication, but it cannot eradicate latent viral reservoirs in HIV-1/AIDS patients. A dual-punch approach that combines gene editing with targeted drugs could be the trick we need if the latest mouse study is any indication, it demonstrated a successful cure in five out of 13 transgenic mice, leaving many excited.
HIV virus is a true master in disguise, transforming its appearance as it proliferates inside the human body. Even if all else fails, the virus can hide its genetic template inside our own DNA, ready to emerge when the heat dies off. Thanks to this talent for staying low, the best we can do is strike with an arsenal of pharmaceuticals designed to keep the deadly pathogen underground, preventing it from emerging and ravaging the body’s immune system. Mice infected with HIV ended up virus-free after US researchers were able to remove it from their cells for the first time, according to a study published last week. Researchers at Temple University in Pennsylvania and the University of Nebraska developed a two-step approach to eliminate the AIDS-causing virus from the genomes of the mice.
In the first part of the treatment, a special slow-release form of antiretroviral medication (known as LASER ART) was administered. The drugs halt the progress of HIV by targeting the virus’ life-cycle, but they do not eliminate it. In the second part, scientists used CRISPR-cas9 gene editing to remove HIV DNA from infected cells. Over a third of the mice examined in the study had no signs of HIV DNA in their cells following the combination treatment. The research team at Temple University said that the main take away from the study is that when the two methods are used together, they can be used to produce a cure for HIV infection. We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year. People who are infected with HIV have a high risk of developing AIDS, which leads to a progressive failure of the immune system. There is currently no cure for HIV/AIDS, but recent research has shown that antiretroviral medication can suppress the virus. Over 35 million people have died around the world since the HIV/AIDS epidemic emerged in the 1980s. While the number of AIDS-related deaths are falling, the number of new infections worldwide remains high at 1.8 million new cases each year, according to the World Health Organization.
In popular usage, “CRISPR” (pronounced “crisper”) is shorthand for “CRISPR-Cas9.” CRISPRs are specialized stretches of DNA. The protein Cas9 (or “CRISPR-associated”) is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA. CRISPR (clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found within the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments from viruses that have previously infected the prokaryote and are used to detect and destroy DNA from similar viruses during subsequent infections. Hence these sequences play a key role in the antiviral defense system of prokaryotes.
Cas9 (or CRISPR-associated protein 9) is an enzyme that uses CRISPR sequences as a guide to recognize and cleave specific strands of DNA that is complementary to the CRISPR sequence. Cas9 enzymes together with CRISPR sequences form the basis of a technology known as CRISPR Cas9 that can be used to edit genes within organisms. This editing process has a wide variety of applications including basic biological research, development of biotechnology products, and treatment of diseases. The discovery of the CRISPR/Cas9 gene editing technology has provided renewed hope for alternative suppressive therapies and possible elimination of HIV-1 integrated provirus DNA from the genomes of infected individuals. However, even though this strategy has been somewhat successful in vitro laboratory cell models, editing of HIV-1 DNA in cells and tissues that support viral reservoirs in vivo has been challenging. Accordingly, recent strategies have employed targeted vectors to deliver CRISPR/Cas9 complexes directly to infected subjects. However, the recherché team is optimistic, it’s also aware that it has a lot of ground to cover between mice and humans. Things that work in mice, may not work in men. The limitations of any mouse work have to do with the species, how the drug is administered, the distribution, which is a lot easier than a man or a woman. With hope recherché will succeed to cure HIV in human beings very shortly as they done in mice.
— The writer is retired officer of Sindh Govt.
