Tag Archives: HIV

Hit and run gene therapy?

The approach looks promising but there’s a still long way to go before this ‘simpler, gentler’ approach to gene therapy will make its way into any treatments. From an August 30, 2017 news item on Nanowerk,

A new biomedical tool using nanoparticles that deliver transient gene changes to targeted cells could make therapies for a variety of diseases — including cancer, diabetes and HIV — faster and cheaper to develop, and more customizable.

The tool, developed by researchers at Fred Hutchinson Cancer Research Center and tested in preclinical models, is described in a paper published August 30 [2017] in Nature Communications.

This animation demonstrates the approach,

Biodegradable nanoparticles (orange) carry short-lived gene therapy to specific cells (light teal). Animation by Kimberly Carney / Fred Hutch News Service

An August 30, 2017 Fred Hutchinson Cancer Research Center (Fred Hutch) news release (from news release received via email; also on EurekAlert) by Sabrina Richards, which originated the news item, elucidates further (Note: Some links and notes have been removed),

“Our goal is to streamline the manufacture of cell-based therapies,” said lead author DR. MATTHIAS STEPHAN [6], a faculty member in the Fred Hutch Clinical Research Division and an expert in developing biomaterials. “In this study, we created a product where you just add it to cultured cells and that’s it — no additional manufacturing steps.”

Stephan and his colleagues developed a nanoparticle delivery system to extend the therapeutic potential of messenger RNA, which delivers molecular instructions from DNA to cells in the body, directing them to make proteins to prevent or fight disease.

The researchers’ approach was designed to zero in on specific cell types — T cells of the immune system and blood stem cells — and deliver mRNA directly to the cells, triggering short-term gene expression. It’s called “hit-and-run” genetic programming because the transient effect of mRNA does not change the DNA, but it is enough to make a permanent impact on the cells’ therapeutic potential.

Stephan and colleagues used three examples in the Nature Communications paper to demonstrate their technology:

* Nanoparticles carried a gene-editing tool to T cells of the immune system that snipped out their natural T-cell receptors, and then was paired with genes encoding a “chimeric antigen receptor” or CAR, a synthetic molecule designed to attack cancer.
* Targeted to blood stem cells, nanoparticles were equipped with mRNA that enabled the stem cells to multiply and replace blood cancer cells with healthy cells when used in bone marrow transplants.
* Nanoparticles targeted to CAR-T cells and containing foxo1 mRNA, which signals the anti-cancer T cells to develop into a type of “memory” cell that is more aggressive and destroys tumor cells more effectively and maintains anti-tumor activity longer.

Other attempts to engineer mRNA into disease-fighting cells have been tricky. The large messenger molecule degrades quickly before it can have an effect, and the body’s immune system recognizes it as foreign — not coming from DNA in the nucleus of the cell — and destroys it.

Stephan and his Fred Hutch collaborators devised a workaround to those hurdles.

“We developed a nanocarrier that binds and condenses synthetic mRNA and protects it from degradation,” Stephan said. The researchers surrounded the nanoparticle with a negatively charged envelope with a targeting ligand attached to the surface so that the particle selectively homes in and binds to a particular cell type.

The cells swallow up the tiny carrier, which can be loaded with different types of manmade mRNA. “If you know from the scientific literature that a signaling pathway works in synergy, you could co-deliver mRNA in a single nanoparticle,” Stephan said. “Every cell that takes up the nanoparticle can express both.”

The approach involves mixing the freeze-dried nanoparticles with water and a sample of cells. Within four hours, cells start showing signs that the editing has taken effect. Boosters can be given if needed. Made from a dissolving biomaterial, the nanoparticles are removed from the body like other cell waste.

“Just add water to our freeze-dried product,” Stephan said. Since it’s built on existing technologies and doesn’t require knowledge of nanotechnology, he intends for it to be an off-the-shelf way for cell-therapy engineers to develop new approaches to treating a variety of diseases.

The approach could replace labor-intensive electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms. All the handling ends up destroying many of the cells, which limits the amount that can be used in treatments for patients.

Gentler to cells, the nanoparticle system developed by the Fred Hutch team showed that up to 60 times more cells survive the process compared with electroporation. This is a critical feature for ensuring enough cells are viable when transferred to patients.

“You can imagine taking the nanoparticles, injecting them into a patient and then you don’t have to culture cells at all anymore,” he said.

Stephan has tested the technology is cultured cells in the lab, and it’s not yet available as a treatment. Stephan is looking for commercial partners to move the technology toward additional applications and into clinical trials where it could be developed into a therapy.

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

Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers by H. F. Moffett, M. E. Coon, S. Radtke, S. B. Stephan, L. McKnight, A. Lambert, B. L. Stoddard, H. P. Kiem, & M. T. Stephan. Nature Communications 8, Article number: 389 (2017) doi:10.1038/s41467-017-00505-8 Published online: 30 August 2017

This paper is open access.

Faster diagnostics with nanoparticles and magnetic phenomenon discovered 170 years ago

A Jan. 19, 2017 news item on ScienceDaily announces some new research from the University of Central Florida (UCF),

A UCF researcher has combined cutting-edge nanoscience with a magnetic phenomenon discovered more than 170 years ago to create a method for speedy medical tests.

The discovery, if commercialized, could lead to faster test results for HIV, Lyme disease, syphilis, rotavirus and other infectious conditions.

“I see no reason why a variation of this technique couldn’t be in every hospital throughout the world,” said Shawn Putnam, an assistant professor in the University of Central Florida’s College of Engineering & Computer Science.

A Jan. 19, 2017 UCF news release by Mark Schlueb, which originated the news item,  provides more technical detail,

At the core of the research recently published in the academic journal Small are nanoparticles – tiny particles that are one-billionth of a meter. Putnam’s team coated nanoparticles with the antibody to BSA, or bovine serum albumin, which is commonly used as the basis of a variety of diagnostic tests.

By mixing the nanoparticles in a test solution – such as one used for a blood test – the BSA proteins preferentially bind with the antibodies that coat the nanoparticles, like a lock and key.

That reaction was already well known. But Putnam’s team came up with a novel way of measuring the quantity of proteins present. He used nanoparticles with an iron core and applied a magnetic field to the solution, causing the particles to align in a particular formation. As proteins bind to the antibody-coated particles, the rotation of the particles becomes sluggish, which is easy to detect with laser optics.

The interaction of a magnetic field and light is known as Faraday rotation, a principle discovered by scientist Michael Faraday in 1845. Putnam adapted it for biological use.

“It’s an old theory, but no one has actually applied this aspect of it,” he said.

Other antigens and their unique antibodies could be substituted for the BSA protein used in the research, allowing medical tests for a wide array of infectious diseases.

The proof of concept shows the method could be used to produce biochemical immunology test results in as little as 15 minutes, compared to several hours for ELISA, or enzyme-linked immunosorbent assay, which is currently a standard approach for biomolecule detection.

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

High-Throughput, Protein-Targeted Biomolecular Detection Using Frequency-Domain Faraday Rotation Spectroscopy by Richard J. Murdock, Shawn A. Putnam, Soumen Das, Ankur Gupta, Elyse D. Z. Chase, and Sudipta Seal. Small DOI: 10.1002/smll.201602862 Version of Record online: 16 JAN 2017

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

This paper is behind a paywall.

Nano-decoy for human influenza A virus

While the implications for this research are exciting, keep in mind that so far they’ve been testing immune-compromised mice. An Oct. 24, 2016 news item on Nanowerk announces the research,

To infect its victims, influenza A heads for the lungs, where it latches onto sialic acid on the surface of cells. So researchers created the perfect decoy: A carefully constructed spherical nanoparticle coated in sialic acid lures the influenza A virus to its doom. When misted into the lungs, the nanoparticle traps influenza A, holding it until the virus self-destructs.

An Oct. 24, 2015 Rensselaer Polytechnic Institute press release by Mary L. Martialay, which originated the news item, describes the research (Note: Links have been removed),

In a study on immune-compromised mice, the treatment reduced influenza A mortality from 100 percent to 25 percent over 14 days. The novel approach, which is radically different from existing influenza A vaccines, and treatments based on neuraminidase inhibitors, could be extended to a host of viruses that use a similar approach to infecting humans, such as Zika, HIV, and malaria. …

“Instead of blocking the virus, we mimicked its target – it’s a completely novel approach,” said Robert Linhardt, a glycoprotein expert and Rensselaer Polytechnic Institute professor who led the research. “It is effective with influenza and we have reason to believe it will function with many other viruses. This could be a therapeutic in cases where vaccine is not an option, such as exposure to an unanticipated strain, or with immune-compromised patients.”

The project is a collaboration between researchers within the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer and several institutions in South Korea including Kyungpook National University. Lead author Seok-Joon Kwon, a CBIS research scientist, coordinated the project across borders, enabling the South Korean institutions to test a drug designed and characterized at Rensselaer. …

To access the interior of a cell and replicate itself, influenza A must first bind to the cell surface, and then cut itself free. It binds with the protein hemagglutinin, and severs that tie with the enzyme neuraminidase. Influenza A produces numerous variations each of hemagglutinin and neuraminidase, all of which are antigens within the pathogen that provoke an immune system response. Strains of influenza A are characterized according to the variation of hemagglutinin and neuraminidase they carry, thus the origin of the familiar H1N1 or H3N2 designations.

Medications to counter the virus do exist, but all are vulnerable to the continual antigenic evolution of the virus. A yearly vaccine is effective only if it matches the strain of virus that infects the body. And the virus has shown an ability to develop resistance to a class of therapeutics based on neuraminidase inhibitors, which bind to and block neuraminidase.

The new solution targets an aspect of infection that does not change: all hemagglutinin varieties of influenza A must bind to human sialic acid. To trap the virus, the team designed a dendrimer, a spherical nanoparticle with treelike branches emanating from its core. On the outermost branches, they attached molecules, or “ligands,” of sialic acid.

The research found that the size of the dendrimer and the spacing between the ligands is integral to the function of the nanoparticle. Hemagglutinin occurs in clusters of three, or “trimers,” on the surface of the virus, and researchers found that a spacing of 3 nanometers between ligands resulted in the strongest binding to the trimers. Once bound to the densely packed dendrimer, viral neuraminidase is unable to sever the link. The coat of the virus contains millions of trimers, but the research revealed that only a few links provokes the virus to discharge its genetic cargo and ultimately self-destruct.

A different approach, using a less structured nanoparticle, had been previously tested in unrelated research, but the nanoparticle selected proved both toxic, and could be inactivated by neuraminidase. The new approach is far more promising.

“The major accomplishment was in designing an architecture that is optimized to bind so tightly to the hemagglutinin, the neuraminidase can’t squeeze in and free the virus,” said Linhardt. “It’s trapped.”

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

Nanostructured glycan architecture is important in the inhibition of influenza A virus infection by Seok-Joon Kwon, Dong Hee Na, Jong Hwan Kwak, Marc Douaisi, Fuming Zhang, Eun Ji Park, Jong-Hwan Park, Hana Youn, Chang-Seon Song, Ravi S. Kane, Jonathan S. Dordick, Kyung Bok Lee, & Robert J. Linhardt. Nature Nanotechnology (2016)  doi:10.1038/nnano.2016.181 Published online 24 October 2016

This paper is behind a paywall.

Possible nanoparticle-based vaccine/microbiocide for herpes simplex virus-2

An April 27, 2016 news item on ScienceDaily describes a new therapeutic and preventative technology for herpes,

An effective vaccine against the virus that causes genital herpes has evaded researchers for decades. But now, researchers from the University of Illinois at Chicago [UIC] working with scientists from Germany have shown that zinc-oxide nanoparticles shaped like jacks can prevent the virus from entering cells, and help natural immunity to develop.

“We call the virus-trapping nanoparticle a microbivac, because it possesses both microbicidal and vaccine-like properties,” says corresponding author Deepak Shukla, professor of ophthalmology and microbiology & immunology in the UIC College of Medicine. “It is a totally novel approach to developing a vaccine against herpes, and it could potentially also work for HIV and other viruses,” he said.

The particles could serve as a powerful active ingredient in a topically-applied vaginal cream that provides immediate protection against herpes virus infection while simultaneously helping stimulate immunity to the virus for long-term protection, explained Shukla.

An April 27, 2016 UIC news release (also on EurekAlert), which originated the news item, provides more context for the work,

Herpes simplex virus-2, which causes serious eye infections in newborns and immunocompromised patients as well as genital herpes, is one of the most common human viruses. According to the Centers for Disease Control and Prevention, about 15 percent of people from ages 14-49 carry HSV-2, which can hide out for long periods of time in the nervous system. The genital lesions caused by the virus increase the risk for acquiring human immunodeficiency virus, or HIV.

“Your chances of getting HIV are three to four times higher if you already have genital herpes, which is a very strong motivation for developing new ways of preventing herpes infection,” Shukla said.

Treatments for HSV-2 include daily topical medications to suppress the virus and shorten the duration of outbreaks, when the virus is active and genital lesions are present. However, drug resistance is common, and little protection is provided against further infections. Efforts to develop a vaccine have been unsuccessful because the virus does not spend much time in the bloodstream, where most traditional vaccines do their work.

The news release goes on to provide technical details,

The tetrapod-shaped zinc-oxide nanoparticles, called ZOTEN, have negatively charged surfaces that attract the HSV-2 virus, which has positively charged proteins on its outer envelope. ZOTEN nanoparticles were synthesized using technology developed by material scientists at Germany’s Kiel University and protected under a joint patent with UIC.

When bound to the nanoparticles, HSV-2 cannot infect cells. But the bound virus remains susceptible to processing by immune cells called dendritic cells that patrol the vaginal lining. The dendritic cells “present” the virus to other immune cells that produce antibodies. The antibodies cripple the virus and trigger the production of customized killer cells that identify infected cells and destroy them before the virus can take over and spread.

The researchers showed that female mice swabbed with HSV-2 and an ointment containing ZOTEN had significantly fewer genital lesions than mice treated with a cream lacking ZOTEN. Mice treated with ZOTEN also had less inflammation in the central nervous system, where the virus can hide out.

The researchers were able to watch immune cells pry the virus off the nanoparticles for immune processing, using high-resolution fluorescence microscopy.

“It’s very clear that ZOTEN facilitates the development of immunity by holding the virus and letting the dendritic cells get to it,” Shukla said.

If found safe and effective in humans, a ZOTEN-containing cream ideally would be applied vaginally just prior to intercourse, Shukla said. But if a woman who had been using it regularly missed an application, he said, she may have already developed some immunity and still have some protection. Shukla hopes to further develop the nanoparticles to work against HIV, which like HSV-2 also has positively charged proteins embedded in its outer envelope.

ZOTEN particles are uniform in size and shape, making them attractive for use in other biomedical applications. The novel flame transport synthesis technology used to make them allows large-scale production, said Rainer Adelung, professor of nanomaterials at Kiel University. And, because no chemicals are used, the production process is green.

Adelung hopes to begin commercial production of ZOTEN through a startup company that will be run jointly with his colleagues at UIC.

Here’s an image of the particles, courtesy of UIC,

Zinc oxide tetrapod nanoparticles. Credit: Deepak Shukla

Zinc oxide tetrapod nanoparticles. Credit: Deepak Shukla

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

Intravaginal Zinc Oxide Tetrapod Nanoparticles as Novel Immunoprotective Agents against Genital Herpes by Thessicar E. Antoine, Satvik R. Hadigal, Abraam M. Yakoub, Yogendra Kumar Mishra, Palash Bhattacharya, Christine Haddad, Tibor Valyi-Nagy, Rainer Adelung, Bellur S. Prabhakar, and Deepak Shukla. The Journal of Immunology April 27, 2016 1502373  doi: 10.4049/jimmunol.1502373 Published online before print April 27, 2016

This paper is behind a paywall.

One final comment, it’s a long from a mouse vagina in this study to a human one.

Lab tests show silver nanoparticles in cream blocks HIV entry for up to 72 hours

Since at least 2005 (the article reference will be given later in this posting), researchers have been aware that silver nanoparticles can block the HIV virus from entering a cell. The latest work in this area has resulted in a vaginal cream laced with silver nanoparticles according to a Jan. 28, 2014 news item on ScienceDaily,

Lara Villegas [Humberto Lara Villegas, specialist in nanoparticles and virology from the University of Monterrey, Mexico (UDEM)] explained that HIV makes its entry to immune cells (CD4) of the organism with the aid of a protein known as GP120, which allows the virus adherence to the cells. This same principle is used by silver nanoparticles to attach themselves to this protein and block it, turning the virus inactive.

The Mexican researcher informed that the cream has been tested in samples of human tissue and has proven the efficiency of silver nanoparticles to avoid the transmission of the virus through cervical mucous membrane.

The Jan. 28, 2014 Investigación y Desarrollo news release (on the Alpha Gallileo website), which originated the news item, provides additional details from Lara Villegas’ perspective,

The researcher from UDEM, who has worked in Israel and The United States, assured that after applied, the cream starts to work in less than a minute, and has an effective protection of up to 72 hours.

Given that the function of this product is the inactivation of the virus, although this is a vaginal cream, will also protect the sexual partner.

“Normally – he highlighted-, the medication used against the virus act within the cell to avoid its replication. This is a very different case, given that the nanoparticle goes directly against the HIV and no longer allows its entry to the cell”.

So far, no toxicity of the silver nanoparticles has been reported, although he added that research is yet to be performed to evaluate the possible side effects of silver properties.

“Right now, I am certain that this microbicide is going to avoid the virus entering the organism, but I cannot yet assure that is totally harmless, because the clinical trials are a long and expensive process”, the researched added.

He exposed that the use of gels are usually accompanied by irritation, which favors the entry of the virus, which is why the cream was enriched with an anti-inflammatory effect.

Currently, with the obtained results, researchers will proceed to perform experimentation in mice that accept human cells, to later begin with human clinical trials.

He added that this cream could prevent the transmition of other sexually acquired virus like the Human Papilloma Virus (HPV). Likewise, he considered that silver nanoparticles could be used to combat bacteria transmitted the same way.

As promised here’s a citation for and a link to the 2005 paper; I haven’t found any references in my admittedly brief search for a paper about this latest work,,

Interaction of silver nanoparticles with HIV-1 by Jose Luis Elechiguerra, Justin L Burt, Jose R Morones, Alejandra Camacho-Bragado, Xiaoxia Gao, Humberto H Lara, and Miguel Jose Yacaman. Journal of Nanobiotechnology 2005, 3:6  doi:10.1186/1477-3155-3-6

This paper is open access.

Here’s  the Investigación y Desarrollo website which seems to act as a hub for research in Mexico. Note: You will need Spanish language skills to fully utilize this site.

Bee venom, HIV (human immunodeficiency virus), and targeted nanoparticles

Researchers at Washington University School of Medicine in St Louis (Missouri, US) have found a way to use nanoparticles impregnated with bee venom to hopelessly damage HIV (human immunodeficiency virus) in laboratory tests, according to a Mar. 7, 2013 news release on EurekAlert,

Nanoparticles carrying a toxin found in bee venom can destroy human immunodeficiency virus (HIV) while leaving surrounding cells unharmed, researchers at Washington University School of Medicine in St. Louis have shown. The finding is an important step toward developing a vaginal gel that may prevent the spread of HIV, the virus that causes AIDS.

“Our hope is that in places where HIV is running rampant, people could use this gel as a preventive measure to stop the initial infection,” says Joshua L. Hood, MD, PhD, a research instructor in medicine.

 Nanoparticles (purple) carrying melittin (green) fuse with HIV (small circles with spiked outer ring), destroying the virus’s protective envelope. Molecular bumpers (small red ovals) prevent the nanoparticles from harming the body’s normal cells, which are much larger in size.  Credit: Joshua L. Hood, MD, PhD (downloaded from: http://news.wustl.edu/news/Pages/25061.aspx

Nanoparticles (purple) carrying melittin (green) fuse with HIV (small circles with spiked outer ring), destroying the virus’s protective envelope. Molecular bumpers (small red ovals) prevent the nanoparticles from harming the body’s normal cells, which are much larger in size. Credit: Joshua L. Hood, MD, PhD (downloaded from: http://news.wustl.edu/news/Pages/25061.aspx

Dexter Johnson in his Mar. 8, 2013 posting on Nanoclast (IEEE [Institute of Electrical and Electronics Engineers] blog) contextualizes this research with links to other related research along with his comments about this latest work (Note: A link has been removed),

The research, which was published in the journal Antiviral Therapy (“Cytolytic nanoparticles attenuate HIV-1 infectivity”), employed a nanoparticle that had previously been abandoned when it proved ineffective for delivering oxygen to blood cells. But in its new role, carrying the toxin melittin, a poison found in bee venom, it is extremely effective at breaking down the essential structure of HIV.

The Washington University in Saint Louis Mar. 7, 2013 news release (and origin for EurekAlert news release) written by Julia Evangelou Strait provides details about the research,

Bee venom contains a potent toxin called melittin that can poke holes in the protective envelope that surrounds HIV, and other viruses. Large amounts of free melittin can cause a lot of damage. Indeed, in addition to anti-viral therapy, the paper’s senior author, Samuel A. Wickline, MD, the J. Russell Hornsby Professor of Biomedical Sciences, has shown melittin-loaded nanoparticles to be effective in killing tumor cells.

The new study shows that melittin loaded onto these nanoparticles does not harm normal cells. That’s because Hood added protective bumpers to the nanoparticle surface. When the nanoparticles come into contact with normal cells, which are much larger in size, the particles simply bounce off. HIV, on the other hand, is even smaller than the nanoparticle, so HIV fits between the bumpers and makes contact with the surface of the nanoparticle, where the bee toxin awaits.

“Melittin on the nanoparticles fuses with the viral envelope,” Hood says. “The melittin forms little pore-like attack complexes and ruptures the envelope, stripping it off the virus.”

According to Hood, an advantage of this approach is that the nanoparticle attacks an essential part of the virus’ structure. In contrast, most anti-HIV drugs inhibit the virus’s ability to replicate. But this anti-replication strategy does nothing to stop initial infection, and some strains of the virus have found ways around these drugs and reproduce anyway.

“We are attacking an inherent physical property of HIV,” Hood says. “Theoretically, there isn’t any way for the virus to adapt to that. The virus has to have a protective coat, a double-layered membrane that covers the virus.”

Beyond prevention in the form of a vaginal gel, Hood also sees potential for using nanoparticles with melittin as therapy for existing HIV infections, especially those that are drug-resistant. The nanoparticles could be injected intravenously and, in theory, would be able to clear HIV from the blood stream.

While this work was done in cells in a laboratory environment, Hood and his colleagues say the nanoparticles are easy to manufacture in large enough quantities to supply them for future clinical trials.

Here’s a citation and link to the paper,

Joshua L Hood, Andrew P Jallouk, Nancy Campbell, Lee Ratner, Samuel A Wickline. Cytolytic nanoparticles attenuate HIV-1 infectivity. Antiviral Therapy. Vol. 19: 95 – 103. 2013

The article is behind a paywall.

Home pregnancy tests inspire simple diagnostics containing gold nanoparticles

PhD student Kyryl Zagorovsky and Professor Warren Chan of the University of Toronto’s Institute of Biomaterials and Biomedical Engineering (IBBME) have created a rapid diagnostic biosensor according to a Feb. 28, 2013 news item on phys.org,

A diagnostic “cocktail” containing a single drop of blood, a dribble of water, and a dose of DNA powder with gold particles could mean rapid diagnosis and treatment of the world’s leading diseases in the near future. …

The recent winner of the NSERC E.W.R. Steacie Memorial Fellowship, Professor Chan and his lab study nanoparticles: in particular, the use of gold particles in sizes so small that they are measured in the nanoscale. Chan and his group are working on custom-designing nanoparticles to target and illuminate cancer cells and tumours, with the potential of one day being able to deliver drugs to cancer cells.

But it’s a study recently published in Angewandte Chemie that’s raising some interesting questions about the future of this relatively new frontier of science.

Zagorovsky’s rapid diagnostic biosensor will allow technicians to test for multiple diseases at one time with one small sample, and with high accuracy and sensitivity. The biosensor relies upon gold particles in much the same vein as your average pregnancy test. With a pregnancy test, gold particles turn the test window red because the particles are linked with an antigen that detects a certain hormone in the urine of a pregnant woman.

(Until now, I’d never thought about how a pregnancy test actually works and always assumed it was similar to a litmus paper test of acid.) The University of Toronto’s Feb. 28, 2013 news release, which originated the news item, describes the technology in more detail,

Currently, scientists can target a particular disease by linking gold particles with DNA strands. When a sample containing the disease gene (e.g., Malaria) is present, it clumps the gold particles, turning the sample blue.

Rather than clumping the particles together, Zagorovsky immerses the gold particles in a DNA-based enzyme solution (DNA-zyme) that, when the disease gene is introduced, ‘snip’ the DNA from the gold particles, turning the sample red.

“It’s like a pair of scissors,” said Zagorovsky. “The target gene activates the scissors that cut the DNA links holding gold particles together.”

The advantage is that far less of the gene needs to be present for the solution to show noticeable colour changes, amplifying detection. A single DNA-zyme can clip up to 600 ‘links’ between the target genes.

Just a single drop from a biological sample such as saliva or blood can potentially be tested in parallel, so that multiple diseases can be tested in one sitting.

But the team has also demonstrated that [it] can transform the testing solution into a powder, making it light and far easier to ship than solutions, which degrade over time. Powder can be stored for years at a time, and offers hope that the technology can be developed into efficient, cheap, over-the-counter tests for diseases such as HIV and malaria for developing countries, where access to portable diagnostics is a necessity. [emphases mine]

I think the fact that the testing solution can be made into powder is exciting news. Medical technologies can be wonderful but if they require special handling and training (e.g., a standard vaccine is in a solution which needs to be refrigerated [that’s expensive in some parts of the world] and someone who is specially trained has to administer the injection) then they’re confined to the few who have access and can afford it.

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

A Plasmonic DNAzyme Strategy for Point-of-Care Genetic Detection of Infectious Pathogens by Kyryl Zagorovsky, and Dr. Warren C. W. Chan. Angewandte Chemie International Edition DOI: 10.1002/anie.201208715 Article first published online: 10 FEB 2013

Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This article is behind a paywall.

ETA Mar. 1, 2013 10:42 am PST: I made a quick change to the title. Hopefully this one makes more sense than the first one did.

Zimbabwe and its international nanotechnology center, ZINC

A Sept.24, 2012 news item on Nanowerk provides information about a new nanotechnology center in Zimbabwe,

With 14 percent of Zimbabwe’s population living with HIV/AIDS and tuberculosis as a co-infection, the need for new drugs and new formulations of available treatments is crucial.

To address these issues, two of the University at Buffalo’s [UB] leading research centers, the Institute for Lasers, Photonics and Biophotonics (ILPB), and the New York State Center of Excellence in Bioinformatics and Life Sciences have signed on to launch the Zimbabwe International Nanotechnology Center (ZINC) — a national nanotechnology research program — with the University of Zimbabwe (UZ) and the Chinhoyi University of Technology (CUT).

This collaborative program will initially focus on research in nanomedicine and biosensors at UZ and energy at CUT. ZINC has grown out of the NIH [US National Institute of Health] Fogarty International Center, AIDS International Training and Research Program (AITRP) that was awarded to UB and UZ in 2008 to conduct HIV research training and build research capacity in Zimbabwe and neighboring countries in southern Africa.

I decided to find out more about Zimbabwe and found a map and details in a Wikipedia essay,

Location of Zimbabwe within the African Union (accessed Sept. 24, 2012 from the Wikipedia essay on Zimbabwe)

Zimbabwe (… officially the Republic of Zimbabwe) is a landlocked country located in Southern Africa, between the Zambezi and Limpopo rivers. It is bordered by South Africa to the south, Botswana to the southwest, Zambia and a tip of Namibia to the northwest (making this area a quadripoint) and Mozambique to the east. The capital is Harare. Zimbabwe achieved recognised independence from Britain in April 1980, following a 14-year period as an unrecognised state under the predominantly white minority government of Rhodesia, which unilaterally declared independence in 1965. Rhodesia briefly reconstituted itself as black-majority ruled Zimbabwe Rhodesia in 1979, but this order failed to gain international acceptance.

Zimbabwe has three official languages: English, Shona and Ndebele.

Getting back to Zimbabwe, Alan on the Science Business website posted on Sept. 24, 2012 about ZINC and the partnership (excerpted from the posting),

University at Buffalo in New York and two universities in the southern African nation of Zimbabwe will collaborate on a new nanotechnology research program in pharmacology. University of Zimbabwe in Harare and the Chinhoyi University of Technology in Mashonaland West, working with Buffalo’s Institute for Lasers, Photonics, and Biophotonics, along with New York State Center of Excellence in Bioinformatics and Life Sciences also on the Buffalo campus, will establish the Zimbabwe International Nanotechnology Center (ZINC).

ZINC aims to develop an international research and training capability in nanotechnology that advances the field as contributor to Zimbabwe’s economic growth. The collaboration is expected to focus on research in nanomedicine and biosensors for health care at University of Zimbabwe, while the Chinhoyi University of Technology partnership will conduct research related to energy.

The University of Buffalo Sept. 24, 2012 news release provides more details,

The UB ILPB and TPRC [Translational Pharmacy Research Core] collaboration recognized that the fields of pharmacology and therapeutics have increasingly developed links with emerging areas within the field of nanosciences in an attempt to develop tissue/organ targeted strategies that will lead to disease treatment and eradication. Research teams will focus on emerging technologies, initially focused in nanobiotechnology and nanomedicine for health care.

“Developing nanoformulations for HIV and tuberculosis diagnostics and therapeutics, as well as new tuberculosis drug development, are just a few of the innovative strategies to address these co-infections that this research collaboration can provide,” said Morse [Gene D. Morse, PharmD, Professor of Pharmacy Practice, associate director of the New York State Center of Excellence in Bioinformatics and Life Sciences and director of the Translational Pharmacy Research Core {TPRC}].

“In addition, the development of new nanotechnology-related products will jumpstart the economy and foster new economic initiatives in Zimbabwe that will yield additional private-public partnerships.”

Morse says that the current plans for a “Center of Excellence” in clinical and translational pharmacology in Harare at UZ will create a central hub in Africa, not just for Zimbabwe but for other countries to gain new training and capacity building in many exciting aspects of nanotechnology as well.

Good luck to ZINC and its partners!

University of Liverpool announces work on HIV/AIDS nanomedicines

Given that Vancouver (Canada) is a world centre for HIV/AIDS  research (courtesy of Dr. Julio Montaner‘s work), the Aug. 30, 2012 news item on Nanowerk  about nanomedicines being developed at the University of Liverpool, which are less toxic therapeutic alternatives to current HIV/AIDS medications, caught my eye. From the news item,

Scientists at the University of Liverpool are leading a £1.65 million project to produce and test the first nanomedicines for treating HIV/AIDS.

There aren’t many details about how they are going to produce these nanomedicines other than what’s in these paragraphs in the Aug. 30, 2012 University of Liverpool news release,

The research project, funded by the [UK] Engineering and Physical Sciences Research Council (EPSRC), aims to produce cheaper, more effective medicines which have fewer side effects and are easier to give to newborns and children.

The new therapy options were generated by modifying existing HIV treatments, called antiretrovirals (ARVs). The University has recently produced ARV drug particles at the nanoscale which potentially reduce the toxicity and variability in the response different patients have to therapies. Drug nanoparticles have been shown to allow smaller doses in other disease areas which opens up possibilities to reduce drug side-effects and the risk of drug resistance. Nanoscale objects are less than one micron in size – a human hair is approximately 80 microns in diameter.

If I read the news release for this project rightly, there aren’t any immediate plans for making these nanomedicines widely available for treatment (from the University of Liverpool news release),

The project aims to deliver highly valuable data within three years and provide a platform for continual development and testing during that time

Elsewhere in the news release they do mention clinical trials,

Professor Andrew Owen, from the University’s Department of Molecular and Clinical Pharmacology, added: “We have integrated an assessment of pharmacology and safety early in the research and this has allowed us to rapidly progress lead options for clinical trials. The work has been conducted with the Medical Research Council (MRC) Centre for Drug Safety Science also based at the University.”

“Our data so far looks really exciting, offering the potential to reduce the doses required to control the HIV virus.  This work builds on initiatives by Médecins Sans Frontières and other groups to seek ways to improve ARV therapy and could have real benefits for the safety of ARVs globally. Importantly we also hope to reduce the costs of therapy for resource-limited countries where the burden of disease is highest.”

Interestingly, the other mention of taking this medicine into the field is in a  photo caption for the research team’s other featured member,

Professor Steve Rannard: “This project is the first step towards taking nanomedicine options out of our labs and into the clinic”

Good luck to them all!

French scientists focus optical microscopes down to 30 nm

In fact, the French scientists are using two different imaging techniques to arrive at a resolution of 30 nm for their optical microscopes, according to the May 18, 2012 news item on Nanowerk.

Researchers from the Institut Pasteur and CNRS [Centre national de la recherche scientifique] have set up a new optical microscopy approach that combines two recent imaging techniques in order to visualize molecular assemblies without affecting their biological functions, at a resolution 10 times better than that of traditional microscopes. Using this approach, they were able to observe the AIDS virus and its capsids (containing the HIV genome) within cells at a scale of 30 nanometres, for the first time with light.

More specifically,

A study coordinated by Dr Christophe Zimmer (Institut Pasteur/CNRS), in collaboration with Dr Nathalie Arhel within the lab headed by Pr Pierre Charneau (Institut Pasteur/CNRS), shows that the association of two recent imaging techniques helps obtain unique images of molecular assemblies of HIV-1 capsids, with a resolution around 10 times better than that of traditional microscopes. This new approach, which uses super-resolution imaging and FlAsH labeling, does not affect the virus’ ability to self-replicate. It represents a major step forward in molecular biology studies, enabling the visualisation of microbial complexes at a scale of 30 nm without affecting their function.

The newly developed approach combines super-resolution PALM imaging and fluorescent FlAsH labeling. PALM imaging relies on the acquisition of thousands of low-resolution images, each of which showing only a few fluorescent molecules. The molecular positions are then calculated with high accuracy by computer programs and compiled into a single high-resolution image. FlAsH labeling involves the insertion of a 6-amino-acid peptide into the protein of interest. The binding of the FlAsH fluorophore to the peptide generates a fluorescent signal, thereby enabling the visualization of the protein. For the first time, researchers have combined these two methods in order to obtain high-resolution images of molecular structures in either fixed or living cells.

The researchers have supplied an image illustrating the difference between the conventional and new techniques will allow them to view (from the May 16, 2012 press release  [communiqué de presses] on the CNRS website),

© Institut Pasteur Reconstruction optique super-résolutive de la morphologie du VIH. L'image du dessous montre la distribution moyenne de l'enzyme intégrase observée par FlAsH-PALM. La résolution de cette technique (~30 nm) permet de retrouver la taille et la forme conique de la capside. Pour comparaison, la résolution de la microscopie conventionnelle (~200-300 nm), illustrée par l'image du dessus, ne permet pas une description détaillée de cette structure.

The conventional 200 – 300 nm resolution is shown at the top while the new 30 nm resolution achieved by combining the new techniques is shown below. This new technique has already allowed scientists to disprove a popular theory about the AIDS virus, from the May 18, 2012 news item on Nanowerk,

This new method has helped researchers visualise the AIDS Virus and localise its capsids in human cells, at a scale of 30 nm. Capsids are conical structures which contain the HIV genome. These structures must dismantle in order for the viral genome to integrate itself into the host cell’s genome. However, the timing of this disassembly has long been debated. According to a prevailing view, capsids disassemble right after infection of the host cell and, therefore, do not play an important role in the intracellular transport of the virus to the host cell’s nucleus. However, the results obtained by the researchers of the Institut Pasteur and CNRS indicate that numerous capsids remain unaltered until entry of the virus into the nucleus, confirming and strengthening earlier studies based on electron microscopy. Hence, capsids could play a more important role than commonly assumed in the replication cycle of HIV.

I gather excitement about this development is high as the scientists are suggesting that ‘microscopy’ could be known as ‘nanoscopy’ in the future.