Tag Archives: Daniel G Anderson

Editing the genome with CRISPR ((clustered regularly interspaced short palindromic repeats)-carrying nanoparticles

MIT (Massachusetts Institute of Technology) researchers have developed a new nonviral means of delivering CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene therapy according to a November 13, 2017 news item on Nanowerk,

In a new study, MIT researchers have developed nanoparticles that can deliver the CRISPR genome-editing system and specifically modify genes in mice. The team used nanoparticles to carry the CRISPR components, eliminating the need to use viruses for delivery.

Using the new delivery technique, the researchers were able to cut out certain genes in about 80 percent of liver cells, the best success rate ever achieved with CRISPR in adult animals.

In a new study, MIT researchers have developed nanoparticles that can deliver the CRISPR genome-editing system and specifically modify genes, eliminating the need to use viruses for delivery. Image: MIT News

A November 13, 2017 MIT news release (also on EurekAlert), which originated the news item, provides more details about the research and a good description of and comparison between using a viral system and using a nanoparticle-based system to deliver CRISPR-CAS9,

“What’s really exciting here is that we’ve shown you can make a nanoparticle that can be used to permanently and specifically edit the DNA in the liver of an adult animal,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

One of the genes targeted in this study, known as Pcsk9, regulates cholesterol levels. Mutations in the human version of the gene are associated with a rare disorder called dominant familial hypercholesterolemia, and the FDA recently approved two antibody drugs that inhibit Pcsk9. However these antibodies need to be taken regularly, and for the rest of the patient’s life, to provide therapy. The new nanoparticles permanently edit the gene following a single treatment, and the technique also offers promise for treating other liver disorders, according to the MIT team.

Anderson is the senior author of the study, which appears in the Nov. 13 [2017] issue of Nature Biotechnology. The paper’s lead author is Koch Institute research scientist Hao Yin. Other authors include David H. Koch Institute Professor Robert Langer of MIT, professors Victor Koteliansky and Timofei Zatsepin of the Skolkovo Institute of Science and Technology [Russia], and Professor Wen Xue of the University of Massachusetts Medical School.

Targeting disease

Many scientists are trying to develop safe and efficient ways to deliver the components needed for CRISPR, which consists of a DNA-cutting enzyme called Cas9 and a short RNA that guides the enzyme to a specific area of the genome, directing Cas9 where to make its cut.

In most cases, researchers rely on viruses to carry the gene for Cas9, as well as the RNA guide strand. In 2014, Anderson, Yin, and their colleagues developed a nonviral delivery system in the first-ever demonstration of curing a disease (the liver disorder tyrosinemia) with CRISPR in an adult animal. However, this type of delivery requires a high-pressure injection, a method that can also cause some damage to the liver.

Later, the researchers showed they could deliver the components without the high-pressure injection by packaging messenger RNA (mRNA) encoding Cas9 into a nanoparticle instead of a virus. Using this approach, in which the guide RNA was still delivered by a virus, the researchers were able to edit the target gene in about 6 percent of hepatocytes, which is enough to treat tyrosinemia.

While that delivery technique holds promise, in some situations it would be better to have a completely nonviral delivery system, Anderson says. One consideration is that once a particular virus is used, the patient will develop antibodies to it, so it couldn’t be used again. Also, some patients have pre-existing antibodies to the viruses being tested as CRISPR delivery vehicles.

In the new Nature Biotechnology paper, the researchers came up with a system that delivers both Cas9 and the RNA guide using nanoparticles, with no need for viruses. To deliver the guide RNAs, they first had to chemically modify the RNA to protect it from enzymes in the body that would normally break it down before it could reach its destination.

The researchers analyzed the structure of the complex formed by Cas9 and the RNA guide, or sgRNA, to figure out which sections of the guide RNA strand could be chemically modified without interfering with the binding of the two molecules. Based on this analysis, they created and tested many possible combinations of modifications.

“We used the structure of the Cas9 and sgRNA complex as a guide and did tests to figure out we can modify as much as 70 percent of the guide RNA,” Yin says. “We could heavily modify it and not affect the binding of sgRNA and Cas9, and this enhanced modification really enhances activity.”

Reprogramming the liver

The researchers packaged these modified RNA guides (which they call enhanced sgRNA) into lipid nanoparticles, which they had previously used to deliver other types of RNA to the liver, and injected them into mice along with nanoparticles containing mRNA that encodes Cas9.

They experimented with knocking out a few different genes expressed by hepatocytes, but focused most of their attention on the cholesterol-regulating Pcsk9 gene. The researchers were able to eliminate this gene in more than 80 percent of liver cells, and the Pcsk9 protein was undetectable in these mice. They also found a 35 percent drop in the total cholesterol levels of the treated mice.

The researchers are now working on identifying other liver diseases that might benefit from this approach, and advancing these approaches toward use in patients.

“I think having a fully synthetic nanoparticle that can specifically turn genes off could be a powerful tool not just for Pcsk9 but for other diseases as well,” Anderson says. “The liver is a really important organ and also is a source of disease for many people. If you can reprogram the DNA of your liver while you’re still using it, we think there are many diseases that could be addressed.”

“We are very excited to see this new application of nanotechnology open new avenues for gene editing,” Langer adds.

The research was funded by the National Institutes of Health (NIH), the Russian Scientific Fund, the Skoltech Center, and the Koch Institute Support (core) Grant from the National Cancer Institute.

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

Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing by Hao Yin, Chun-Qing Song, Sneha Suresh, Qiongqiong Wu, Stephen Walsh, Luke Hyunsik Rhym, Esther Mintzer, Mehmet Fatih Bolukbasi, Lihua Julie Zhu, Kevin Kauffman, Haiwei Mou, Alicia Oberholzer, Junmei Ding, Suet-Yan Kwan, Roman L Bogorad, Timofei Zatsepin, Victor Koteliansky, Scot A Wolfe, Wen Xue, Robert Langer, & Daniel G Anderson. Nature Biotechnology doi:10.1038/nbt.4005 Published online: 13 November 2017

This paper is behind a paywall.

Tightening the skin (and protecting it and removing wrinkles, temporarily)

“It’s an invisible layer that can provide a barrier, provide cosmetic improvement, and potentially deliver a drug locally to the area that’s being treated. Those three things together could really make it ideal for use in humans,” Daniel Anderson says. Photo: Melanie Gonick/MIT

“It’s an invisible layer that can provide a barrier, provide cosmetic improvement, and potentially deliver a drug locally to the area that’s being treated. Those three things together could really make it ideal for use in humans,” Daniel Anderson says. Photo: Melanie Gonick/MIT

It almost looks like he’s peeling off his own skin and I imagine that’s the secret to this polymer’s success. A May 9, 2016 news item on phys.org describes the work being done at the Massachusetts Institute of Technology (MIT) and elsewhere with collaborators,

Scientists at MIT, Massachusetts General Hospital, Living Proof, and Olivo Labs have developed a new material that can temporarily protect and tighten skin, and smooth wrinkles. With further development, it could also be used to deliver drugs to help treat skin conditions such as eczema and other types of dermatitis.

A May 9, 2016 MIT news release (also on EurekAlert), which originated the news item, provides more detail,

The material, a silicone-based polymer that could be applied on the skin as a thin, imperceptible coating, mimics the mechanical and elastic properties of healthy, youthful skin. In tests with human subjects, the researchers found that the material was able to reshape “eye bags” under the lower eyelids and also enhance skin hydration. This type of “second skin” could also be adapted to provide long-lasting ultraviolet protection, the researchers say.

“It’s an invisible layer that can provide a barrier, provide cosmetic improvement, and potentially deliver a drug locally to the area that’s being treated. Those three things together could really make it ideal for use in humans,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

Anderson is one of the authors of a paper describing the polymer in the May 9 online issue of Nature Materials. Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, is the paper’s senior author, and the paper’s lead author is Betty Yu SM ’98, ScD ’02, former vice president at Living Proof. Langer and Anderson are co-founders of Living Proof and Olivo Labs, and Yu earned her master’s and doctorate at MIT.

Mimicking skin

As skin ages, it becomes less firm and less elastic — problems that can be exacerbated by sun exposure. This impairs skin’s ability to protect against extreme temperatures, toxins, microorganisms, radiation, and injury. About 10 years ago, the research team set out to develop a protective coating that could restore the properties of healthy skin, for both medical and cosmetic applications.

“We started thinking about how we might be able to control the properties of skin by coating it with polymers that would impart beneficial effects,” Anderson says. “We also wanted it to be invisible and comfortable.”

The researchers created a library of more than 100 possible polymers, all of which contained a chemical structure known as siloxane — a chain of alternating atoms of silicon and oxygen. These polymers can be assembled into a network arrangement known as a cross-linked polymer layer (XPL). The researchers then tested the materials in search of one that would best mimic the appearance, strength, and elasticity of healthy skin.

“It has to have the right optical properties, otherwise it won’t look good, and it has to have the right mechanical properties, otherwise it won’t have the right strength and it won’t perform correctly,” Langer says.

The best-performing material has elastic properties very similar to those of skin. In laboratory tests, it easily returned to its original state after being stretched more than 250 percent (natural skin can be elongated about 180 percent). In laboratory tests, the novel XPL’s elasticity was much better than that of two other types of wound dressings now used on skin — silicone gel sheets and polyurethane films.

“Creating a material that behaves like skin is very difficult,” says Barbara Gilchrest, a dermatologist at MGH and an author of the paper. “Many people have tried to do this, and the materials that have been available up until this have not had the properties of being flexible, comfortable, nonirritating, and able to conform to the movement of the skin and return to its original shape.”

The XPL is currently delivered in a two-step process. First, polysiloxane components are applied to the skin, followed by a platinum catalyst that induces the polymer to form a strong cross-linked film that remains on the skin for up to 24 hours. This catalyst has to be added after the polymer is applied because after this step the material becomes too stiff to spread. Both layers are applied as creams or ointments, and once spread onto the skin, XPL becomes essentially invisible.

High performance

The researchers performed several studies in humans to test the material’s safety and effectiveness. In one study, the XPL was applied to the under-eye area where “eye bags” often form as skin ages. These eye bags are caused by protrusion of the fat pad underlying the skin of the lower lid. When the material was applied, it applied a steady compressive force that tightened the skin, an effect that lasted for about 24 hours.

In another study, the XPL was applied to forearm skin to test its elasticity. When the XPL-treated skin was distended with a suction cup, it returned to its original position faster than untreated skin.

The researchers also tested the material’s ability to prevent water loss from dry skin. Two hours after application, skin treated with the novel XPL suffered much less water loss than skin treated with a high-end commercial moisturizer. Skin coated with petrolatum was as effective as XPL in tests done two hours after treatment, but after 24 hours, skin treated with XPL had retained much more water. None of the study participants reported any irritation from wearing XPL.

“I think it has great potential for both cosmetic and noncosmetic applications, especially if you could incorporate antimicrobial agents or medications,” says Thahn Nga Tran, a dermatologist and instructor at Harvard Medical School, who was not involved in the research.

Living Proof has spun out the XPL technology to Olivo Laboratories, LLC, a new startup formed to focus on the further development of the XPL technology. Initially, Olivo’s team will focus on medical applications of the technology for treating skin conditions such as dermatitis.


This video supplied by MIT shows how to apply the polymer and offers a description and demonstration of its properties once applied,

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

An elastic second skin by Betty Yu, Soo-Young Kang, Ariya Akthakul, Nithin Ramadurai, Morgan Pilkenton, Alpesh Patel, Amir Nashat, Daniel G. Anderson, Fernanda H. Sakamoto, Barbara A. Gilchrest, R. Rox Anderson & Robert Langer. Nature Materials (2016) doi:10.1038/nmat4635 Published online 09 May 2016

This paper is behind a paywall.

One final comment, I wonder who’s lining up to invest in this product.

Emory University’s Shuming Nie discusses Iron Man 3 and nanotechnology and researchers develop an injectable nano-network

I have written about Iron Man 3 before (my May 11, 2012 posting) in the context of its nanotechnology inspirations, specifically, the Extremis Armor. For anyone not familiar with the story, I have a few bits which will bring you up to speed before getting to Shuming Nie’s commentary and some recent research into injectable nano-networks, which seems highly relevant to the Iron Man 3 discourse. First, here’s an excerpt from my May 11, 2012 posting,

In a search for Extremis, I found out that this story reboots the Iron Man mythology by incorporating nanotechnology and alchemy to create a new armor, the Extremis Armor, from the Extremis Armor website (I strongly suggest going to the website and reading the full text which includes a number of illustrative images if you find this sort of thing interesting),

When a bio-tech weapon of mass destruction was unleashed, Tony Stark threw himself onto the bleeding edge between science and alchemy, combining nanotechnology and his Iron Man armor.  The result, which debuted in Iron Man, Vol. IV, issue 5, was the Extremis Armor, Model XXXII, Mark I, which made him the most powerful hero in the world–but not without a price.

There were two key parts to this Extremis-enhanced suit.  The first part is the golden Undersheath, the protective interface between Stark’s nervous system and the second chief part, the External Suit Devices (ESDs), a.k.a. the red armor plating.

The Undersheath to the Iron Man suit components was super-compressed and stored in the hollows of Stark’s bones. The sheath material exited through skeletal pores and slid between all cells to self-assemble a new “skin” around him.  This skin provides a complete interface to the Iron Man suit components and can perform numerous other functions. (The process in reverse withdrew the Undersheath back into these specially modified areas of Tony Stark’s bone marrow tissue.)

The Undersheath is a nano-network that incorporates peptide-peptide logic (PPL), a molecular computational system made of superconducting plastic impregnated molecular chains. [my emphasis added for May.6.13 posting]  The PPL handles, among other things: memory, critical logic paths, comparative “truth” tables, automatic response look-up tables, data storage, communication, and external sensing material interface.

The lattice assembly is a stress-compression truss with powered interstitial joints.  This can surround the PPL material and guide it through Stark’s body.  This steerable, motile lattice framework is commanded by the PPL molecule computational mentality.  The metallic component to the lattice is a controlled mimetic artifact that can take on the characteristics of most elements.  Even unusual combinations of behaviors such as extreme hardness and flexibility.

The combination of the two nano-scale materials allows for a very dense non-traditional computer that can change the fabric of its design in very powerful ways. The incorporation of the Undersheath in Stark’s entire nervous system renders reflex-level computer responses to pan-spectrum stimuli.

Anthony Stark’s Bio/Metalo-Mimetic Material concept is a radical departure from the traditional solid-state underpinnings of his prior Iron Man suit designs.  Making use of nano-scale assembly technology, “smart” molecules can be made atom by atom. The design allows for simple computers to be linked into a massive parallel computer that synthesizes human thought protocols.

The External Suit Devices (ESDs), the red armor plates, were made via mega-nano technology that has assembled atoms into large, discreet effectors.  This allows for the plates to be collapsable to very small volumes for easy storage and carried in Stark’s briefcase. The ESDs were commanded by the Undersheath and were self-powered by high-capacity Kasimer plates.  They were equipped with large arrays of nano-fans that allow flight.  Armoring-up was done by drawing the suit to Stark via a vectored repulsor field, just lightly pushing them from different angles.

The armor’s memory-metal technology renders it lightweight and flexible while not in use, but extremely durable when polarized.  The armor was strong, of course, but it could be made even stronger by rerouting repulsor input to reinforce the armor’s mass.

Stark’s skin is now a part of the suit, when engaged.  [emphasis mine] Comfort is relative because the suit rapidly responds to any discomfort, from impacts to high temperatures, from itching to scratching.  The suit’s protocols include semi-autonomy when needed.  Where Stark ends and the suit begins is flexible.  The exact nature of the artificial Extremis Virus is not known (especially because Stark recompiled the dose, then tweaked the nutrients and suspended metals, radically altering Maya Hansen’s [the character Rebecca Hall will reputedly play] formulations).  The effect it has had on Stark’s body is to allow the presence of so much alien material within his body without trauma.

Because of the bio-interface between Tony and the armor, he could utilize the suit to its fullest potential and also instantly access computers and any digital system worldwide at the speed of thought.  He was biologically integrated with his armor, one with it, imbued with unprecedented powers and abilities.  He channeled and processed data, emergency signals, and satellite reconnaissance from every law enforcement, military, and intelligence service in the world–in his head.  He could send electronic signals and make phone calls with his mind.  He could see through satellites.  Plus he had the ability to transmit whatever he saw (from his visual cortex) to other people’s display screens.  The computer’s cybernetic link enables him to operate all of the armor’s functions, as well as providing a remote link to other computers (as Stark is now part of the armor this connection is seamless).  The armor’s system was connected to the global mainframe via StarkTech servers.

I also like this more generalized description of the technology in the Wikipedia essay on Extemis Comics (Note: A link has been removed),

Extremis has been referred to as a “virus” constantly since the story. The verbatim description offered by its inventor Maya Hansen, goes: “…Extremis is a super-soldier solution. It’s a bio-electronics package, fitted into a few billion graphite nanotubes and suspended in a carrier fluid. [emphasis mine] A magic bullet, like the original super-soldier serum—all fitted into a single injection. It hacks the body’s repair center—the part of the brain that keeps a complete blue print of the human body. When we’re injured, we refer to that area of the brain to heal properly. Extremis rewrites the repair center. In the first stage, the body essentially becomes an open wound. The normal human blueprint is being replaced with the Extremis blueprint. The brain is being told the body is wrong. Extremis protocol dictates that the subject be placed on life support and intravenously fed nutrients at this point. For the next two or three days, the patient remains unconscious within a cocoon of scabs. (…) Extremis uses the nutrients and body mass to grow new organs. Better ones…”

A Postmedia movie reviewer, Katherine Monk noted this about the plot in her May 3, 2013 review of Iron Man 3 ,

Apparently, back in the early days of genetic engineering, a brilliant, zit-faced scientist (Guy Pearce) offered Tony a piece of a lucrative patent that had the potential to alter the human body, and even regenerate amputated limbs.

Tony walked away from the offer as well as the pretty girl (Rebecca Hall) who worked for the genetic engineer, but in the opening sequence, we see the technology was successfully developed and tested. It makes people superhuman, but it can also make them spontaneously combust, leaving great craters and human casualties behind.

Now for the video commentary, Dr. Shuming Nie, Biomedical Engineering at Emory University, offers some scientific insight into the science and the fiction of ‘extremis’ as per Iron Man 3 in his YouTube video,

Keeping on the science theme,  researchers at North Carolina State University (NCSU) and other institutions announced an injectable nano-network for diabetics in a May 3, 2013 news release on EurekAlert,

In a promising development for diabetes treatment, researchers have developed a network of nanoscale particles that can be injected into the body and release insulin when blood-sugar levels rise, maintaining normal blood sugar levels for more than a week in animal-based laboratory tests. The work was done by researchers at North Carolina State University, the University of North Carolina at Chapel Hill, the Massachusetts Institute of Technology and Children’s Hospital Boston.

“We’ve created a ‘smart’ system that is injected into the body and responds to changes in blood sugar by releasing insulin, effectively controlling blood-sugar levels,” says Dr. Zhen Gu, lead author of a paper describing the work and an assistant professor in the joint biomedical engineering program at NC State and UNC Chapel Hill. “We’ve tested the technology in mice, and one injection was able to maintain blood sugar levels in the normal range for up to 10 days.”

Here’s how the smart system is achieved,

The new, injectable nano-network is composed of a mixture containing nanoparticles with a solid core of insulin, modified dextran and glucose oxidase enzymes. When the enzymes are exposed to high glucose levels they effectively convert glucose into gluconic acid, which breaks down the modified dextran and releases the insulin. The insulin then brings the glucose levels under control. The gluconic acid and dextran are fully biocompatible and dissolve in the body.

Each of these nanoparticle cores is given either a positively charged or negatively charged biocompatible coating. The positively charged coatings are made of chitosan (a material normally found in shrimp shells), while the negatively charged coatings are made of alginate (a material normally found in seaweed).

When the solution of coated nanoparticles is mixed together, the positively and negatively charged coatings are attracted to each other to form a “nano-network.” Once injected into the subcutaneous layer of the skin, the nano-network holds the nanoparticles together and prevents them from dispersing throughout the body. Both the nano-network and the coatings are porous, allowing blood – and blood sugar – to reach the nanoparticle cores.

“This technology effectively creates a ‘closed-loop’ system that mimics the activity of the pancreas in a healthy patient, releasing insulin in response to glucose level changes,” Gu says. “This has the potential to improve the health and quality of life of diabetes patients.”

For anyone who’s interested in researching further, heres’ a citation for and a link to the paper,

Injectable Nano-Network for Glucose-Mediated Insulin Delivery by Zhen Gu, Alex A. Aimetti, Qun Wang, Tram T. Dang, Yunlong Zhang, Omid Veiseh, Hao Cheng, Robert S. Langer, and Daniel G. Anderson. ACS Nano, Article ASAP DOI: 10.1021/nn400630x Publication Date (Web): May 2, 2013

Copyright © 2013 American Chemical Society

The paper is behind a paywall. Meanwhile, there are discussions about moving these injectable nano-networks into human clinical trials. As Nie notes, Iron Man 3 hints at new medical technologies which will be achievable in the next 10 or so years, although we may have to wait 100 to 150 years for  Extremis armor.

Gluing blood vessels with mussel goo

The University of British Columbia [UBC] Dec. 11, 2012 news release states,

A University of British Columbia researcher has helped create a gel – based on the mussel’s knack for clinging to rocks, piers and boat hulls – that can be painted onto the walls of blood vessels and stay put, forming a protective barrier with potentially life-saving implications.

Co-invented by Assistant Professor Christian Kastrup while a postdoctoral student at the Massachusetts Institute of Technology, the gel is similar to the amino acid that enables mussels to resist the power of churning water. The variant that Kastrup and his collaborators created, described in the current issue of the online journal PNAS [Proceeings of the National Academy of Sciences of the US] Early Edition, can withstand the flow of blood through arteries and veins.

Here’s the citation and a link to the article (which is behind a paywall),

Painting blood vessels and atherosclerotic plaques with an adhesive drug depot by Christian J. Kastrup, Matthias Nahrendorf, Jose Luiz Figueiredo, Haeshin Lee, Swetha Kambhampati, Timothy Lee, Seung-Woo Cho, Rostic Gorbatov, Yoshiko Iwamoto, Tram T. Dang, Partha Dutta, Ju Hun Yeon, Hao Cheng, Christopher D. Pritchard, Arturo J. Vegas, Cory D. Siegel, Samantha MacDougall, Michael Okonkwo, Anh Thai, James R. Stone, Arthur J. Coury, Ralph Weissleder, Robert Langer, and Daniel G. Anderson.  PNAS, December 11, 2012 DOI: 10.1073/pnas.1217972110

For those of a more technical turn of mind, here’s the abstract (from PNAS),

The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques.

The news release describes the work layperson’s terms,

The gel’s “sheer strength” could shore up weakened vessel walls at risk of rupturing – much like the way putty can fill in dents in a wall, says Kastrup, a member of the Department of Biochemistry and Molecular Biology and the Michael Smith Laboratories.

By forming a stable barrier between blood and the vessel walls, the gel could also prevent the inflammation that typically occurs when a stent is inserted to widen a narrowed artery or vein; that inflammation often counteracts the opening of the vessel that the stent was intended to achieve.

The widest potential application would be preventing the rupture of blood vessel plaque. When a plaque ruptures, the resulting clot can block blood flow to the heart (triggering a heart attack) or the brain (triggering a stroke). Mice treated with a combination of the gel and an anti-inflammatory steroid had more stable plaque than a control group of untreated mice.

“By mimicking the mussel’s ability to cling to objects, we created a substance that stays in place in a very dynamic environment with high flow velocities,” says Kastrup, a member of UBC’s Centre for Blood Research.

Robert Langer, one of the paper’s co-authors, was mentioned here in an Aug. 27, 2012 posting about nanoelectronics, tissue engineering, and medicine.

Don’t kill bacteria, uninvite them

The relentless campaign against bacteria has had some unintended consequences, we’ve made bacteria more resistant and more virulent. Researchers at the University of Nottingham (UK) have taken a different approach from attempting to eradicate or kill; they’ve discovered a class of polymers that ‘uninvites’ bacteria from their surfaces. From the Aug. 13, 2012 news item on ScienceDaily,

Using state-of-the-art technology, scientists at The University of Nottingham have discovered a new class of polymers that are resistant to bacterial attachment. These new materials could lead to a significant reduction in hospital infections and medical device failures.

Medical device associated infections can lead to systemic infections or device failure, costing the NHS £1bn a year. Affecting many commonly used devices including urinary and venous catheters — bacteria form communities known as biofilms. This ‘strength in numbers approach’ protects them against the bodies’ natural defences and antibiotics.

Experts in the Schools of Pharmacy and Molecular Medical Sciences, have shown that when the new materials are applied to the surface of medical devices they repel bacteria and prevent them forming biofilms.

There’s a video of the scientists discussing their work on this new class of polymers,

In order to find this new class of polymers, the scientists had to solve another problem first. From the Aug. 12, 2012 University of Nottingham press release,

Researchers believed there were new materials that could resist bacteria better but they had to find them. This meant screening thousands of different chemistries and testing their reaction to bacteria — a challenge which was beyond conventional materials development or any of our current understanding of the interaction of micro-organisms with surfaces.

The discovery has been made with the help of experts from the Massachusetts Institute of Technology (MIT) — who initially developed the process by which thousands of unique polymers can now be screened simultaneously.

Professor Alexander said: “This is a major scientific breakthrough — we have discovered a new group of structurally related materials that dramatically reduce the attachment of pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli). We could not have found these materials using the current understanding of bacteria-surface interactions. The technology developed with the help of MIT means that hundreds of materials could be screened simultaneously to reveal new structure-property relationships. In total thousands of materials were investigated using this high throughput materials discovery approach leading to the identification of novel materials resisting bacterial attachment. This could not have been achieved using conventional techniques.”

Once they found this new class of polymers, researchers tested for effectiveness (from the Aug. 12, 2012 university press release),

These new materials prevent infection by stopping biofilm formation at the earliest possible stage — when the bacteria first attempt to attach themselves to the device. In the laboratory experts were able to reduce the numbers of bacteria by up to 96.7per cent — compared with a commercially available silver containing catheter — and were effective at resisting bacterial attachment in a mouse implant infection model. By preventing bacterial attachment the body’s own immune system can kill the bacteria before they have time to generate biofilms.

You can read more about this work in the paper the researchers have published (as well as, the news item on ScienceDaily or the University of Nottingham press release for more accessible explanations). You will need to get past a paywall (from the news item on ScienceDaily),

Andrew L Hook, Chien-Yi Chang, Jing Yang, Jeni Luckett, Alan Cockayne, Steve Atkinson, Ying Mei, Roger Bayston, Derek J Irvine, Robert Langer, Daniel G Anderson, Paul Williams, Martyn C Davies, Morgan R Alexander. Combinatorial discovery of polymers resistant to bacterial attachment. Nature Biotechnology, 2012; DOI: 10.1038/nbt.2316

This research reminded me of Sharklet, a product being developed in the US for use in hospitals. Designed to mimic sharkskin, the product discourages bacteria from settling on its surface. It was featured in my Feb. 10, 2011 posting.