Tag Archives: Hong Liu

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.

Nano- and neuro- together for nanoneuroscience

This is not the first time I’ve posted about nanotechnology and neuroscience (see this April 2, 2013 piece about then new brain science initiative in the US and Michael Berger’s  Nanowerk Spotlight article/review of an earlier paper covering the topic of nanotechnology and neuroscience).

Interestingly, the European Union (EU) had announced its two  $1B Euro research initiatives, the Human Brain Project and the Graphene Flagship (see my Jan. 28, 2013 posting about it),  months prior to the US brain research push. For those unfamiliar with the nanotechnology effort, graphene is a nanomaterial and there is high interest in its potential use in biomedical technology, thus partially connecting both EU projects.

In any event, Berger is highlighting a nanotechnology and neuroscience connection again in his Oct. 18, 2017 Nanowerk Spotlight article, or overview of, a new paper, which updates our understanding of the potential connections between the two fields (Note: A link has been removed),

Over the past several years, nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience and brain activity mapping.

A review paper in Advanced Functional Materials (“Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping”) summarizes the basic concepts associated with neuroscience and the current journey of nanotechnology towards the study of neuron function by addressing various concerns on the significant role of nanomaterials in neuroscience and by describing the future applications of this emerging technology.

The collaboration between nanotechnology and neuroscience, though still at the early stages, utilizes broad concepts, such as drug delivery, cell protection, cell regeneration and differentiation, imaging and surgery, to give birth to novel clinical methods in neuroscience.

Ultimately, the clinical translation of nanoneuroscience implicates that central nervous system (CNS) diseases, including neurodevelopmental, neurodegenerative and psychiatric diseases, have the potential to be cured, while the industrial translation of nanoneuroscience indicates the need for advancement of brain-computer interface technologies.

Future Developing Arenas in Nanoneuroscience

The Brain Activity Map (BAM) Project aims to map the neural activity of every neuron across all neural circuits with the ultimate aim of curing diseases associated with the nervous system. The announcement of this collaborative, public-private research initiative in 2013 by President Obama has driven the surge in developing methods to elucidate neural circuitry. Three current developing arenas in the context of nanoneuroscience applications that will push such initiative forward are 1) optogenetics, 2) molecular/ion sensing and monitoring and 3) piezoelectric effects.

In their review, the authors discuss these aspects in detail.

Neurotoxicity of Nanomaterials

By engineering particles on the scale of molecular-level entities – proteins, lipid bilayers and nucleic acids – we can stereotactically interface with many of the components of cell systems, and at the cutting edge of this technology, we can begin to devise ways in which we can manipulate these components to our own ends. However, interfering with the internal environment of cells, especially neurons, is by no means simple.

“If we are to continue to make great strides in nanoneuroscience, functional investigations of nanomaterials must be complemented with robust toxicology studies,” the authors point out. “A database on the toxicity of materials that fully incorporates these findings for use in future schema must be developed. These databases should include information and data on 1) the chemical nature of the nanomaterials in complex aqueous environments; 2) the biological interactions of nanomaterials with chemical specificity; 3) the effects of various nanomaterial properties on living systems; and 4) a model for the simulation and computation of possible effects of nanomaterials in living systems across varying time and space. If we can establish such methods, it may be possible to design nanopharmaceuticals for improved research as well as quality of life.”

“However, challenges in nanoneuroscience are present in many forms, such as neurotoxicity; the inability to cross the blood-brain barrier [emphasis mine]; the need for greater specificity, bioavailability and short half-lives; and monitoring of disease treatment,” the authors conclude their review. “The nanoneurotoxicity surrounding these nanomaterials is a barrier that must be overcome for the translation of these applications from bench-to-bedside. While the challenges associated with nanoneuroscience seem unending, they represent opportunities for future work.”

I have a March 26, 2015 posting about Canadian researchers breaching the blood-brain barrier and an April 13, 2016 posting about US researchers at Cornell University also breaching the blood-brain barrier. Perhaps the “inability” mentioned in this Spotlight article means that it can’t be done consistently or that it hasn’t been achieved on humans.

Here’s a link to and a citation for the paper,

Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping by Anil Kumar, Aaron Tan, Joanna Wong, Jonathan Clayton Spagnoli, James Lam, Brianna Diane Blevins, Natasha G, Lewis Thorne, Keyoumars Ashkan, Jin Xie, and Hong Liu. Advanced Functional Materials Volume 27, Issue 39, October 19, 2017 DOI: 10.1002/adfm.201700489 Version of Record online: 14 AUG 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

I took a look at the authors’ information and found that most of these researchers are based in  China and in the UK, with a sole researcher based in the US.