Tag Archives: Bioengineering

Creating the life-saving Nanopatch

Featured image above: creator of the Nanopatch, Professor Mark Kendall

Professor Mark Kendall was all set for a career in aerodynamics when he met a man with an unusual idea: he wanted to use rocket technology to fire vaccines into the skin. Intrigued, Kendall accepted the man’s offer to work at Oxford University, where together with others they developed the ‘gene gun’ – a device that used aerodynamic principles to deliver vaccines to the skin.

That was almost 20 years ago. Kendall has since moved back to Australia and pushed beyond the gene gun technology, creating the Nanopatch, a new and unique way to administer life-saving vaccines that is safer and more effective than using a needle and syringe.

The Nanopatch is a tiny piece of silicon, covered on one side with up to 20,000 microscopic projections per square centimetre. Each of these projections is coated in a dry vaccine. When the patch is applied, these projections deliver the vaccine just below the top layer of the skin, which is abundant in immune cells. Within about a minute, the vaccine becomes wet in the cellular environment and is released. 

 Animal testing has shown that the Nanopatch delivers similarly protective immune responses as the needle and syringe, with significantly lower doses of vaccine. Using dry vaccines also means there is no need for refrigeration. Being needle-free, there is mitigated risk of cross-contamination or injuries. Needle-phobic people can also rejoice: the patch delivery method promises to be painless.
“The Nanopatch has the potential to completely change the way vaccines are delivered and address ongoing problems in the global push for vaccines in the developing world,” says Kendall, Group Leader of The Australian Institute for Bioengineering and Nanotechnology at The University of Queensland.

From aerodynamics to immunology 

Originally a mechanical engineer with a PhD in hypervelocity aerodynamics – “I was researching high-speed wind tunnels for interplanetary missions” – Kendall’s interest in immunology stemmed from his time at Oxford working on the gene gun.

Immunologists had discovered there were thousands of immune cells just under the surface of the skin. Instead of injecting deep into muscle where there are fewer immune cells, why not administer vaccines to the skin? There was only one problem: the technology to effectively do this did not exist – until Kendall came along.

“As an engineer with a knowledge of immunology, I looked at the scale of the cells, their spatial position and how quickly they moved,” says Kendall.

“That fresh thinking allowed me to come up with the idea of using an array of nano-projections to deliver vaccines to those cells. For the array to work, you need a base on which to attach the projections and that was the silicon patch.”

More effective vaccines that don’t need refrigeration

The Nanopatch has two major advantages over traditional vaccination methods. The first is improved immunogenicity. In 2015, Kendall’s team, in collaboration with the World Health Organization (WHO) and the US Centres for Disease Control and Prevention, tested an inactivated poliovirus vaccine on rats using the Nanopatch. They found they needed 40 times less vaccine to generate the same functional immune response as the needle and syringe.

“Many of the new-generation vaccines are expensive, multi-dose medicines that are difficult to make,” says Kendall. “The Nanopatch, when proven in humans, has tremendous potential to reduce manufacturing costs because we will need less vaccine to induce a protective immune response.”

Smaller than a postage stamp and covered in vaccine-coated microscopic projections, the Nanopatch promises to save the lives of millions of people worldwide by giving them access to safe, effective and needle-free vaccinations.

Kendall hopes the Nanopatch can become a vehicle to make vaccines work better in the developing world. 

The Nanopatch has been tested in animals on vaccines for influenza, HPV, polio, malaria, HSV-2, chikungunya, West Nile virus and pneumococcus – all diseases plaguing developing nations. 

Of the 14 million people who die of infectious diseases every year, the majority are in developing countries, where people are not able to receive effective vaccines that exist for others, or they die from diseases that still do not have adequate vaccination methods. 

“The Nanopatch could potentially help on both fronts,” says Kendall. “It can bridge that ‘last mile’ to get effective vaccines to people who aren’t receiving them, and through its improved immunogenicity, could help candidate vaccines for diseases such as malaria to get over the line and be effective.” It may also be possible for people to self-administer the vaccine.

Moreover, unlike liquid vaccines that need to be kept cold from production to application, the Nanopatch does not require refrigeration. Lab tests have shown the dry vaccine can be stored at 23 degrees Celsius for more than a year without any loss of activity – a significant benefit in regions where vaccines have to travel long distances to reach their destination and where there may be no electricity to keep them cold.

Nanopatch trials are underway

In 2011, Kendall founded Vaxxas to develop and commercialise the Nanopatch, raising A$15 million in first-round funding – one of Australia’s largest-ever investments in a startup biotechnology company. Four years later, it raised A$25 million, the proceeds of which was used to advance a series of clinical programs and develop a pipeline of new vaccine products for major diseases.

Vaxxas has also forged a partnership with American pharmaceutical company Merck to evaluate, develop and commercialise the Nanopatch for vaccine candidates. In 2014, Vaxxas was selected as a World Economic Forum Technology Pioneer based on the potential of the Nanopatch to improve health on a global scale.

The Nanopatch is currently undergoing clinical trials. The WHO will also conduct clinical tests to determine the utility of the Nanopatch for polio vaccinations. Concurrently, Vaxxas is determining if the Nanopatch can be manufactured in large numbers at low cost. All things going well, Kendall says the Nanopatch may be commercially available by 2020.

For his pioneering work, Kendall has received a raft of awards, most recently the 2016 Dr John Dixon Hughes Medal for Medical Research Innovation and the 2016 CSL Young Florey Medal, one of Australia’s highest science honours.

But Kendall will not rest until the Nanopatch is in the field. 

“Vaccines will continually be improved; there will be new vaccines coming out for diseases that don’t currently have adequate vaccination strategies and improved vaccines for the ones that do,” he says.

“I’m not going to be satisfied until we’ve rolled the Nanopatch out, taken it out of the lab and got it to people in large numbers, particularly the people who need it the most.”

Mark Kendall with the Nanopatch

Find out more about The Australian Institute for Bioengineering and Nanotechnology at the University of Queensland.

Find out more about Vaxxas.

– Charmaine Teoh

This article was first published by Australia Unlimited. Read the original article here.

Is it possible to reverse ageing?

Featured image above: reverse ageing.

Since successful genome sequencing was first announced in 2000 by geneticists Craig Venter and Francis Collins, the cost of mapping DNA’s roughly three billion base pairs has fallen exponentially. Venter’s effort to sequence his genome cost a reported US$100 million and took nine months. In March, Veritas Genetics announced pre-orders for whole genome sequencing, plus interpretation and counselling, for US$999.

Another genetics-based start-up, Human Longevity Inc (HLI), believes abundant, relatively affordable sequencing and collecting other biological data will revolutionise healthcare delivery. Founded by Venter, stem cell specialist Robert Hariri and entrepreneur Peter Diamandis, it claims to have sequenced more human genomes than the rest of the world combined, with 20,000 last year, a goal of reaching 100,000 this year and over a million by 2020.

HLI offers to “fully digitise” a patient’s body – including genotypic and phenotypic data collection, and MRI, brain vascular system scans – under its US$25,000 Health Nucleus service. Large-scale machine learning is applied to genomes and phenotypic data, following the efforts at what Venter has called “digitising biology”.

The claim is that artificial intelligence (AI) can predict maladies before they emerge, with “many” successes in saving lives seen in the first year alone. The company’s business includes an FDA-approved stem cell therapy line and individualised medicines. The slogan “make 100 the new 60” is sometimes mentioned in interviews with founders. Their optimism is not isolated. Venture capitalist Peter Thiel admits he takes human growth hormone to maintain muscle mass, confident the heightened risk of cancer will be dealt with completely by a cancer cure, and plans to live to 120.

“We understand what the surgeon needs and we embed that in an algorithm so it’s full automated.”

Bill Maris, CEO of GV (formerly Google Ventures), provocatively said last year that he thinks it’s possible to live to 500. An anit-ageing crusader, biological gerontologist Dr Aubrey de Grey, co-founder and chief science officer of Strategies for Engineered Negligible Senescence (SENS, whose backers include Thiel), has claimed that people alive today might live to 1000.

Longevity expectations are constantly being updated. Consider that, in 1928, American demographer Louis Dublin put the upper limit of the average human lifespan at 64.8. How long a life might possibly last is a complex topic and there’s “some debate”, says Professor of Actuarial Studies at UNSW Michael Sherris.

He says there have been studies examining how long a life could be extended if certain types of mortality, such as cancer, were eliminated, points out Sherris.

“However, humans will still die of something else,” he adds. “The reality is that the oldest person lived to 122.”

Will we see a 1000-year-old human? It isn’t known. What is clear, though, is that efforts to extend health and improve lives have gotten increasingly sophisticated.

The definition of bioengineering has also grown and changed over the years. Now concerning fields including biomaterials, bioinformatics and computational biology, it has expanded with the ability to apply engineering principles at the cellular and molecular level.

Reverse ageing
A team led by Professor Jason Cooper-White at the University of Queensland’s Australian Institute for Biotechnology and Nanotechnology (AIBN) recently published research showing a novel stem cell screening method, a “lab on a chip”, almost. The credit card-sized device looks a boon for productivity. According to AIBN, it is able to run “8,100 experiments at one time”, deliver a five- to ten-fold increase in stem cell differentiation, and decrease the cost of this by 100 to 1,000 by reducing cell media culture used. The Cooper-White Lab focusses on “cardiac and vascular development, disease and regeneration”. Among many awards, Professor Cooper-White last year picked up the Aon Risk Solutions Regenerative Medicine Award. Credit: AIBN

Editing out problems to reverse ageing

What if, further than reading and comprehending the code life is written in, it could also be rewritten as desired? A technique enabling this with better productivity and accuracy than any before it, has gotten many excited about this possibility.

“In terms of speed, it’s probably 10 times as quick as the old technology and is five to 10 times as cheap,” says Professor Robert Brink, Chief Scientist at the Garvan Institute of Medical Research’s MEGA Genome Engineering Facility.

The facility uses the CRISPR/Cas9 process to make genetically-engineered mice for academic and research institute clients. Like many labs, Brink’s facility has embraced CRISPR/Cas9, which has made editing plant and animal DNA so accessible even amateurs are dabbling.

First described in a June 2012 paper in Science, CRISPR/Cas9 is an adaptation of bacteria’s defences against viruses. Using a guide RNA matching a target’s DNA, the Cas9 in the title is an endonuclease that makes a precise cut at the site matching the RNA guide. Used against a virus, the cut degrades and kills it. The triumphant bacteria cell then keeps a piece of viral DNA for later use and identification (described sometimes as like an immunisation card). This is assimilated at a locus in a chromosome known as CRISPR (short for clustered regularly spaced short palindromic repeats).

In DNA more complicated than a virus’s, the cut DNA is able to repair itself, and incorporates specific bits of the new material into its sequence before joining the cut back up. Though ‘off-target’ gene edits are an issue being addressed, the technique has grabbed lots of attention. Some claim it could earn a Nobel prize this year. There is hope it can be used to eventually address gene disorders, such as Beta thalassemias and Huntington’s disease.

“Probably the obvious ones are gene therapy, for humans, and agricultural applications in plants and animals,” says Dr George Church of Harvard Medical School.

Among numerous appointments, Church is Professor of Genetics at Harvard Medical School and founding core faculty member at the Wyss Institute for Biologically Inspired Engineering. Last year, a team led by Dr Church used CRISPR to remove one of the major barriers to pig-human organ transplants – retroviral DNA – in pig embryos.

You can have what are called, ‘universal donors’. That’s being used, for example, in making cells that fight cancer.

“We’re now at the point where it used to be that you would have to have a perfect match between donor and recipient of human cells, but that was because you couldn’t engineer either one of them genetically,” he says. “You can engineer the donor so that it doesn’t cause an immune reaction. Now, you can have what are called, ‘universal donors’. That’s being used, for example, in making T cells that fight cancer – what some of us call CAR-T cells. You can use CRISPR to engineer them so that they’re not only effective against your cancer, but they don’t cause immune complications.”

Uncertainty exists in a number of areas regarding CRISPR (including patent disputes, as well as ethical concerns). However, there is no doubt it has promise.

“I think it will eventually have a great impact on medicine,” believes Brink. “It’s come so far, so quickly already that it’s almost hard to predict… Being able to do things and also being able to ensure everyone it’s safe is another thing, but that will happen.”

And as far as acceptance by the general public? Everything that works to overcome nature seems, well, unnatural, at least at first. Then it’s easier to accept once the benefits of are apparent. Church – who believes we could reverse ageing in five or six years – is hopeful about the future. He also feels the world needs people leery about progress, and who might even throw up a “playing God” argument or two.

“I mean it’s good to have people who don’t drive cars and don’t wear clothes and things like that, [and] it’s good to have people who are anti-technology because they give us an alternative way of thinking about things,” he says.

“[Genetic modification] is now broadly accepted in the sense that in many countries people eat genetically-modified foods and almost all countries, they use genetically-modified bacteria to make drugs like Insulin. I think there are very few people who would refuse to take Insulin just because it’s made in bacteria.”

Reverse ageing
The Australian Centre of Excellence in Electromaterials Science (ACES) at the University of Wollongong, is a leader in biological 3D printing. Alongside three other universities, it offers the world’s first masters degree in biofabrication. The highly-interdisciplinary role of biofabricator “melds technical skills in materials, mechatronics and biology with the clinical sciences” says ACES Director, Professor Gordon Wallace. One of its projects is “layered brain-like structures”. Using layered bio-ink made of carbohydrates and neurons, the work adds to progress on a “bench-top brain”. Such a brain would be hugely useful for new drugs and electroceuticals. Professor Wallace, recently in the news for the BioPen stem cell printer, believes, in the coming years and with regulatory approval, cartilage for preventing arthritis, islet cells to treat diabetes, and stem cells will all be biofabricated treatments. Credit: ACES

A complete mindshift

Extended, healthier lives are all well and good. However, humans are constrained by the upper limits of what our cells are capable of, believes Dr Randal Koene.

For that and other reasons, the Dutch neuroscientist and founder of Carbon Copies is advancing the goal of Substrate Independent Minds (SIM). The most conservative form (relatively speaking) of SIM is Whole Brain Emulation, a reverse-engineering of our grey matter.

“In system identification, you pick something as your black box, a piece of the puzzle small enough to describe by using the information you can glean about signals going in and signals going out,” he explains, adding that the approach is that of mainstream neuroscience. “The system identification approach is used in neuroscience explicitly both in brain-machine interfaces, and in the work on prostheses.”

No brain much more complicated than a roundworm’s has been emulated yet. Its 302 neurons are a fraction of the human brain’s roughly 100 billion.

Koene believes that a drosophila fly, with a connectome of 100,000 or so neurons, could be emulated within the next decade. He is reluctant to predict when this might be achieved for people.

There’s reason for hope, though, with research at University of Southern California’s Center for Neural Engineering pointing the way.

 “The people from the [Theodore] Berger lab at USC, they’ve had some really good results using the system identification approach to make a neural prosthesis,” Koene says.

Koene counts being able to replace the function of part of a brain as the “smallest precursor” to whole brain emulation, with the end goal a mind that can operate without a body.

reverse ageing
Professor Milan Brandt, Technical Director of RMIT’s $25 million Advanced Manufacturing Precinct, has led the university in numerous collaborative projects. These include an Australian-first 3D printed spinal replacement with Anatomics, a vertebral cage for a patient with a deformity and excruciating back pain.  Other endeavours include the university’s provisionally patented Just-In-Time patient-specific bone implant method. To be useful away from its creators, the process – which creates implants with lattice-like mesh structures that emulate the weight and flex of bone – needs to be usable by surgeons with no prior experience with 3D printing. “We understand what the surgeon needs and we embed that in an algorithm so that it’s fully automated,” Dr Martin Leary tells create. Credit: RMIT

 – Simon Lawrence

This article was originally published in the July 2016 issue of create – Engineers Australia‘s member magazine. Read the original article here.

Women in STEM: Mathilde Desselle

Featured image above by Nathan Barden

Desselle is a programme coordinator for outreach for the Community for Open Antimicrobial Drug Discovery (CO-ADD) at The University of Queensland’s Institute for Molecular Bioscience. She is looking for the next antibiotic in engaging academic chemists worldwide in an open-access compound screening program and setting up international partnerships. Desselle has eight years’ experience driving engagement strategies for medical research programs and facilities. She is passionate about finding innovative approaches to drive transformational change and solutions to diagnose, track and treat infectious diseases.

Desselle is a board director for the Queensland-based Women in Technology peak industry body for women in science and technology careers, and for the Tech Girls Movement foundation, promoting positive role models to encourage and raise awareness of STEM careers for girls.

Desselle completed a double Masters degree in bioengineering and business from the Catholic University of Lille and a Masters of International Economics from the University of the Littoral Opal Coast in France in 2008.

What do you think is the most important character trait in a successful scientist?

“I would say having a drive. It takes passion, tenacity, and a vision to lead successful research initiatives, and I believe having an articulate “why” is essential to feed them. Don’t we always go back to what drives us when celebrating successful outcomes and overcoming rejection and failures?”

What is one thing you would change to improve the gender balance in senior ranks of scientists?

“Ending the ‘manel’. I would ask the 32 Australian universities and research institutes who are part of the SAGE pilot, an initiative of the Australian Academy of Science and the Academy of Technological Sciences and Engineering that addresses gender equity in the science, technology, engineering, maths and medicine (STEMM) sectors, to make the following pledge: striving to achieve gender balance in all conferences and panel discussions they are hosting and organising.”

What support structures did/do you have in place that have facilitated your success?

“I will forever be grateful to the mentors who have pushed me outside of my comfort zone. We also have world-class facilities in Australia enabling ground-breaking research and innovative collaborative projects. I am looking for the next antibiotic to combat drug-resistant infections, and it takes advanced scientific, technological and administrative systems to function.”

If at times your confidence is a little shaky, where do you turn?

“I can count on a very supportive network of women and men around me, on their experiences and their expertise. There is always someone I can turn to for addressing concerns or uncertainties. I also practice mindfulness and Harvard Business School social psychologist Professor Amy Cuddy’s “power poses”. Watch her Ted Talk on body language and challenge your inner wonder woman!”

What is your ideal holiday – and do you work on your holiday?

“My ideal holiday is being out horse riding on trails or beaches all day in New Zealand or in the USA. After I get off the saddle, I still follow up on pressing matters, and never lose an occasion to meet or connect with someone I could follow up with for professional matters, so I guess I rarely completely switch off.”

Follow Mathilde Desselle on Twitter: @mathildesselle

This article was first published by Women in Science AUSTRALIA. Read the original article here.