Tag Archives: Temple University

CRISPR/Cas9 used successfully to edit SIV (simian immunodeficiency virus, which is similar to HIV) out of monkey genome

Before reading further please note, the research discussed in this posting is based on animal testing, which many people find highly disturbing.

CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9), or more familiarly CRISPR/Cas9, has been been used to edit simian immunodeficiency virus from infected monkeys’ cells according to a December 2, 2020 article by Matthew Rozsa for Salon.com (Note: Links have been removed),

With multiple coronavirus vaccines being produced as we speak, the COVID-19 pandemic appears to have an end in sight, though the HIV pandemic continues after more than 40 years. That might seem like a head-scratcher: why is HIV, a virus we’ve known about for decades, so much harder to cure than a virus discovered just last year? Part of the reason is that HIV, as a retrovirus, is a more complex virus to vaccinate against than SARS-CoV-2 — hence why a vaccine or other cure has eluded scientists for decades. 

Now, a surprising new study on a related retrovirus shows incredible promise for the potential to develop a cure for HIV, or human immunodeficiency virus. In an article published in the scientific journal Nature Communications, scientists revealed that they had used CRISPR – a genetic technology that can alter DNA and whose developers won the 2020 Nobel Prize in Chemistry [specifically, Jennifer Doudna and Emanuelle Charpentier received the Nobel for developing CRISPR-cas9 or CRISPR/Cas9 not CRISPR alone) — to successfully edit SIV (simian immunodeficiency virus), a virus similar to HIV, out of the genomes of non-human primates.  Specifically, the scientists were able to edit out the SIV genome from rhesus macaque monkeys’ infected cells.

For anyone who’s interested in how CRISPR was developed and the many contributions which have led to the current state-of-the-art for CRISPR gene editing, see the History subsection of Wikipedia’s CRISPR entry.

Getting back to Rozsa’s December 2, 2020 article,

“This study used the CRISPR CaS9 system, which has been described as molecular scissors,” Andrew G. MacLean, PhD, wrote to Salon. MacLean is an associate professor at the Tulane National Primate Research Center and the Department of Microbiology and Immunology at Tulane University School of Medicine and was a senior co-investigator of the study. “It uses a highly specific targeting system to cut out a specific portion of DNA that is necessary for HIV to be able to produce more virus.”

He added, “Our collaborators at in the Khalili Lab at Temple University have developed a method of ‘packaging’ this within a single so-called vector. A vector is a non-disease causing virus that is used as a carrier for the CRISPR CaS9 scissors to get it into the tissues of interest.”

The experiments with SIV are considered to be a gateway to understanding HIV, as HIV is believed to have evolved from SIV, and is genetically similar.

“The rhesus macaque model of HIV/AIDS is the most valuable model to test efficacy of new interventions or approaches for preventing or treating HIV infection, prior to human clinical trials,” Binhua Ling, PhD, associate professor at the Southwest National Primate Research Center, Texas Biomedical Research Institute, wrote to Salon. “This first proof-of-principal [emphasis mine] study on the rhesus macaque model indicates that this virus-vehicle-delivered-CRISPR system can reach many tissue sites of the body, and is able to effectively delete virus DNA in infected cells. This paves the way for applying the same technology to the human body, which could lead to a cure for HIV infection.”

Tricia H. Burdo, PhD, another senior co-investigator on the new study who works at the Lewis Katz School of Medicine at Temple University, explained to Salon by email that “HIV is in a class of viruses (retroviruses) that inserts itself into the DNA of the host, so you can really think of this now as a genetic disease” — in other words, the kind of thing that would be ripe for CRISPR’s scissors-like ability to remove errant or unwanted genetic material. Burdo notes that the CRISPR technology discussed in the article “cuts out this foreign viral gene.”

The study was conducted on eight Rhesus macaque monkeys. That is a very small number to start with and not all of the monkeys received the CRISPR/Cas9 treatment. From the ‘Animals used in the study and ethical statement‘ subsection of the study, “Animals were sacrificed for tissue collection 3 weeks after … .” Leaving aside how anyone may feel about ‘sacrificing …’, three weeks is not a long time for observation.

Should you be interested, there is a November 30, 2020 Tulane University news release announcing the research.

If you want to read the whole study, here’s a link and a citation,

CRISPR based editing of SIV proviral DNA in ART treated non-human primates by Pietro Mancuso, Chen Chen, Rafal Kaminski, Jennifer Gordon, Shuren Liao, Jake A. Robinson, Mandy D. Smith, Hong Liu, Ilker K. Sariyer, Rahsan Sariyer, Tiffany A. Peterson, Martina Donadoni, Jaclyn B. Williams, Summer Siddiqui, Bruce A. Bunnell, Binhua Ling, Andrew G. MacLean, Tricia H. Burdo & Kamel Khalili. Nature Communications volume 11, Article number: 6065 (2020) DOI: https://doi.org/10.1038/s41467-020-19821-7 Published: 27 November 2020

This paper is open access.

As Rozsa notes in his December 2, 2020 article, the Joint United Nations Programme on HIV/AIDS estimates that 32.7 million [24.8 million–42.2 million] people have died from AIDS-related illnesses since the start (1981?) of the epidemic to the end of 2019.

Using nanoparticles to prevent ruptures (heart attacks and/or strokes) in artery walls

This technique from Temple University (Pennsylania, US)  is a long way from ready for general use but it certainly looks promising. From an Oct. 4, 2013 news item on Azonano,

Omar Z. Fisher, assistant professor of bioengineering in Temple’s College of Engineering, has developed a method for linking polyphenols, which are very strong antioxidants, to polymers that can self-assemble into nanoparticles.

Fisher said the project will focus on using these polymers to encapsulate superparamagnetic iron oxide particles (SPIOs), a nano-scale MRI contrasting agent used by his collaborator, Amber Doiron, assistant professor of bioengineering at Binghamton University.

The Oct. 2, 2013 Temple University news release by Preston Moretz, which originated the news item, describes how the nanoparticles will act in the body,

The antioxidant nanoparticles containing the contrasting agent would travel through the blood vessels until they reach atherosclerotic plaque, enabling doctors to diagnose the severity of plaques before they rupture, said Fisher.

“The worse the plaque is, the more likely it is to rupture and give you a clot,” he said. “Because these polymers are made from antioxidants, they are sensitive to oxidative stress, which is more prevalent in more severe plaques.”

Once the oxidative stress destroys the polymers, the MRI contrast agents will be released inside the plaques.

Fisher said doctors would likely prescribe an MRI when a patient was showing some signs of cardiac distress such as fatigue or chest pains.

“During the MRI, the degree of contrast would be visible and indicate to doctors not only that the plaques were there, but the severity of the plaques and how likely they would be to rupture,” he said.

No mention was made of a published paper in either the news item or the news release.