Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

ASU scientists develop new, rapid pipeline for antimicrobials

14.12.2017

High-throughput technology can go from idea to discovery to stockpiling 1,000 doses within a week

With hospitals more often reaching for antibiotics of last resort to fight infections and recent Ebola and Zika outbreaks crossing borders like never before, the worldwide scientific community has been challenged with developing new antimicrobials to safeguard the population.


ASU scientists have recently met a challenge of developing a new class of antimicrobials, called synbodies, to safeguard the population against infectious threats -- all within a week.

Credit: Biodesign Institute, Arizona State University

The research arm of the U.S. Department of Defense, the Defense Advanced Research Program Agency, or DARPA, is known for taking on out-sized challenges such as this. And so, they put out a call for researchers to figure out how to make at least 1000 doses to any unknown pathogen - in a week.

An ASU team was one of the few that rose to this challenge.

"As far as we know we were the only team to figure out how to do this for any pathogen - virus or bacterium," said research leader Stephen Albert Johnston, who directs the ASU Biodesign Institute's Center for Innovations in Medicine and is a professor in the School of Life Sciences. "While the system is designed to create antimicrobials in an extreme emergency - which we hope is never needed - the basic elements can be applied to improve conventional approaches to making anti-infectives.

"My research center thrives on taking on projects most think cannot be done. This challenge was too good not to respond."

Synthetic sentinels

Antibodies are large, Y-shaped proteins produced by the human immune system to ward off foreign invaders. Our bodies mount this defense rapidly, especially if they have seen the invader before, producing the needed antibody within days of infection.

But to make them in the lab, antibodies specific for just one invader can take months, and be an expensive proposition.

Johnston wanted to mimic nature's approach while dramatically reducing the antimicrobial discovery and production time.

For the past decade, Johnston's team has been a pioneer in developing lab-made versions that focus on just the business end of antibodies, critical pathogen recognition elements, called synthetic antibodies, or synbodies.

Synbodies are made from two short protein fragments, called peptides, which are joined together to form a small, antibody-like compound still large enough to do its job.

Chipping away

But even the process of making synbodies typically takes several months.

Synbodies are selected on peptide chips containing a premade set of 10,000 peptides placed in neat rows on a microscope glass slide, called a microarray.

To generate a synbody with antibiotic activity, a solution containing bacteria or viruses can be placed on the microarray.

"Our solution to save time was to pre-screen a large number of pathogens on the microarray and find 100 peptides that would be diverse enough so that any pathogen screened would bind to two or more peptides," said Chris Diehnelt, an associate research professor in Johnston's center who oversaw the lab experiments.

They could stockpile large stocks of these 100 peptides in advance so that 1,000 or more doses of a therapeutic could be quickly produced, screening the best candidates that block a given pathogen. These candidates are then produced in large amounts, purified and tested in mice for acute toxicity so that the whole process is completed in a week.

For their proof-of-concept, they screened a total of 21 different viruses and bacteria against their synbody arrays.

"We found that the majority of the peptides recognized one pathogen," said Diehnelt.

In addition, they tested their system against two unknown pathogens that were not used in the study.

"The data showed that this array can potentially identify binding peptides for any given pathogen," said Diehnelt.

A shot in the arm

"With this approach, dozens or even hundreds of synbodies can be produced in a day," said Johnston.

The best candidates are quickly evaluated both for effective killing and toxicity to humans and can be produced on a large scale.

Finally, their system was tested against two societal scourges and major worldwide health concerns: a potentially pandemic flu strain (H1N1 influenza) as a viral test and a bacterium that causes surgery-related infections, S. epidermidis.

"Our data indicate that a new virus or bacterium can be screened against the small peptide library to discover binding peptides that can be converted into neutralizing antiviral and antibacterial synbodies in a rapid manner," said Diehnelt.

The next steps would be to prepare the final product for an IV delivery, and to scale up the system to produce enough product for a population-wide use ----should the next Ebola, Zika or unanticipated outbreak occur.

"One key, unique feature of our synbody technology is that the same platform can produce synbodies with direct antibiotic or antiviral activity, and we can do it at a fraction of the potential cost as current, commercially produced therapeutic antibodies," said Johnston.

This is good news for saving lives before the next inevitable outbreak occurs.

And for Johnston, who has also spun out companies based on other ASU technologies he has developed or co-developed, it could also mean big business in addition to the potential to save lives. The global therapeutic monoclonal antibody market and cancer therapies are in high demand, with an estimated market size close to $100 billion for 2018.

###

This work was funded by a grant from the Defense Advanced Research Projects Agency (W911NF-10-0299) to professor Stephen Albert Johnston under the 7-Day Biodefense Program.

Media Contact

Joseph Caspermeyer
joseph.caspermeyer@asu.edu
480-258-8972

 @ASU

http://asunews.asu.edu/ 

Joseph Caspermeyer | EurekAlert!

Further reports about: antibiotic bacteria bacterium pathogens peptides therapeutic

More articles from Health and Medicine:

nachricht Graphene nanoflakes: a new tool for precision medicine
19.08.2019 | Schweizerischer Nationalfonds SNF

nachricht A new method of tooth repair? Scientists uncover mechanisms to inform future treatment
09.08.2019 | University of Plymouth

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

Im Focus: Vehicle Emissions: New sensor technology to improve air quality in cities

Researchers at TU Graz are working together with European partners on new possibilities of measuring vehicle emissions.

Today, air pollution is one of the biggest challenges facing European cities. As part of the Horizon 2020 research project CARES (City Air Remote Emission...

Im Focus: Self healing robots that "feel pain"

Over the next three years, researchers from the Vrije Universiteit Brussel, University of Cambridge, École Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI-Paris) and Empa will be working together with the Dutch Polymer manufacturer SupraPolix on the next generation of robots: (soft) robots that ‘feel pain’ and heal themselves. The partners can count on 3 million Euro in support from the European Commission.

Soon robots will not only be found in factories and laboratories, but will be assisting us in our immediate environment. They will help us in the household, to...

Im Focus: Scientists create the world's thinnest gold

Scientists at the University of Leeds have created a new form of gold which is just two atoms thick - the thinnest unsupported gold ever created.

The researchers measured the thickness of the gold to be 0.47 nanometres - that is one million times thinner than a human finger nail. The material is regarded...

Im Focus: Study on attosecond timescale casts new light on electron dynamics in transition metals

An international team of scientists involving the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg has unraveled the light-induced electron-localization dynamics in transition metals at the attosecond timescale. The team investigated for the first time the many-body electron dynamics in transition metals before thermalization sets in. Their work has now appeared in Nature Physics.

The researchers from ETH Zurich (Switzerland), the MPSD (Germany), the Center for Computational Sciences of University of Tsukuba (Japan) and the Center for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

Stanford builds a heat shield just 10 atoms thick to protect electronic devices

19.08.2019 | Information Technology

Researchers demonstrate three-dimensional quantum hall effect for the first time

19.08.2019 | Physics and Astronomy

Catalysts for climate protection

19.08.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>