Category Archives: BioEngineering

Plants engineered to produce therapeutic peptides could provide a cost-effective and sustainable platform for manufacturing drugs.

As a proof of concept, researchers have coaxed a close relative of tobacco,Nicotiana benthamiana, to churn out peptides with antibiotic activity against some of the nastiest pathogens known to medicine, as others had done in the past[1].

But, unlike previous efforts to turn plants into drug-production bioreactors, the scientists also modified their shrubs to express a rat enzyme, called PAM, that enhances the stability and prolongs the activity of antimicrobial peptides.

The resulting plants yielded potent drugs that should cost far less to manufacture than those made via other systems with the added benefit of offering a more environmentally friendly route to drug assembly.

These plants can be grown on a massive scale, providing a reliable and cost-effective source of medicines for people around the world, says bioengineering professor Magdy Mahfouz, who led the study.

We now intend to use this technology to produce a wide range of biologics and therapeutics, adds Shahid Chaudhary, a Ph.D. student in Mahfouzs lab group and the first author of the new report.

The KAUST research team, which included bioengineers Charlotte Hauser and Samir Hamdan, along with microbiologist Pei-Ying Hong and collaborators from Canada, showed that antimicrobial peptides made in this way could kill several dangerous pathogens, including multiple drug-resistant superbugs responsible for some of the deadliest hospital-acquired infections. The antibiotics also proved harmless to mammalian cells, suggesting that they should be safe for human consumption.

Thinking ahead to eventual deployment of the biopharming technique on a massive scale, the researchers showed that their plants were about 3.5-times more efficient at making antibiotics than comparable plants that lack the PAM enzyme modification.

They also added up all the expenses of drug manufacturing and calculated that they could produce 10 milligrams of clinical-grade antimicrobial peptides for less than $0.74 USD much less than the ~$1000 USD cost of production in commercial companies that chemically synthesize peptides and well below the cost of manufacturing in mammalian cells.

Moreover, plant-based drug manufacturing generates none of the hazardous waste associated with other production platforms, thus making it a much greener option for the pharmaceutical industry.

Mahfouz and his colleagues next plan to make other types of therapeutics in the same way.

Large-scale industrial production of therapeutic molecules in plants represents a significant step forward in the democratization of medicine, Mahfouz says. By harnessing the power of molecular biomanufacturing, we can now produce high-quality clinical-grade therapeutics at a fraction of the cost of traditional manufacturing methods.

Nature Communications

Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens

16-Mar-2023

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Using plants as factories for green drug production - EurekAlert

05/12/2023 By Edwin L. Aguirre

One person dies every 34 seconds in the United States from cardiovascular disease, the CDC reports, and this costs the country about $229 billion each year in health care services, medicines and lost productivity due to disability or death.

Cardiac CT scans are an important tool that doctors use to diagnose cardiovascular diseases in patients.

Yu and his co-investigators are developing a new image-reconstruction algorithm based on artificial intelligence (AI) that would effectively freeze the beating heart in CT images within a brief, 60-millisecond time window (one twentieth of a heartbeat).

This would eliminate the blurring movement of the coronary arteries in X-ray images and help doctors analyze plaque buildup on the walls of the arteries, which is the main cause of heart attacks, Yu says.

Moreover, our method will not require patients to hold their breath during the CT exam and will eliminate the need to use beta-blocker drugs to slow down the patients heart rates, he says.

According to Yu, the teams AI-based computational framework would radically improve the image quality of existing CT scanners and would benefit patients who suffer from tachycardia (rapid heartbeat) and arrhythmia (irregular heartbeat) that commonly occur in older adults, many of whom experience atrial fibrillation (rapid, irregular heart rhythm).

Our project will combine two innovative image-processing algorithms compressed sensing and deep learning to reconstruct cardiac CT images at very high resolution and with lower radiation exposure to patients compared to traditional CT scans, Yu notes.

He says their technique could allow them to help build powerful, low-cost cardiac CT scanners, and possibly retrofit older models to perform cardiac CT exams.

Our algorithm could dramatically expand the capability of these systems, allowing higher-quality cardiac CT scans in many underprivileged communities worldwide.

Assisting Yu in the lab research is Yongshun Xu, a fourth-year electrical engineering doctorate student.

Im actively recruiting more postdocs and graduate students, says Yu. I hope to get two postdocs and two Ph.D. students to join the project this fall.

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Researchers Developing AI-Based Technology to Improve Cardiac ... - UMass Lowell

EARLY STEPS What got you interested in science?

I had all sorts of jobs when I was young, from taxi-driving to cocktail waitressing; but these were to pay the rent. Math and science were what made sense to me from an early age. I idolized my father, a nuclear physicist. I obtained a BSc in Mechanical and Aerospace Engineering and worked for a while in the nuclear industry and in solar energy, but my real love turned out to be something I did not even know could be possible until I went to graduate school at age 25: engineering the biological world.

Enzymes are the catalysts responsible for all the wonderful chemistry of the biological world. We would like to use them in human applications, but they are not ideal for this. So, in the 1980s, I started to engineer amino-acid sequences for enzymes that would perform in human applications. Back then, no one knew which sequence would be required to encode a desired function enzymes are complicated. However, evolution can show us how to encode enzymes more effectively. The simple process of mutation and natural selection that has given rise to the rich diversity of the biological world can be harnessed by chemists.

Using newly developed tools in the fields of molecular biology and high-throughput screening, I developed ways to practice evolution by artificial selection for enzymes.

In other words, this is a simple optimization strategy for making random mutations at a low level and screening to find the mutations that can be most beneficial to us. Through various iterations, we find the best-performing steps. Nature is solving all sorts of problems that we throw at her how to degrade plastic bottles, how to degrade pesticides, herbicides, and antibiotics. She creates new enzymes in response to these problems all the time, in real time. With directed evolution, we can do the same create new enzymes in response to new problems.

What excites me most right now is expanding the chemistry of the biological world to compete with human chemists. Making and breaking bonds. All my projects are about sustainability or, bioremediation making things in a cleaner fashion or breaking them down again. I love working with enzymes. Nature has developed a vast array of enzymes that do incredible chemistry, but theres a lot that hasnt been explored yet.

We could have better processes by getting enzymes to do chemistry that would, for instance, dramatically reduce the cost of manufacturing pharmaceuticals by replacing 10 chemical steps with one or two enzymes. One particular example I am proud of is how Merck [a multinational science and technology company] developed an enzyme using directed evolution to make the drug Januvia, which is used to treat diabetes. The initial, unrefined process used toxic metals, with a lot of waste products. Merck has managed to reduce the waste to around one-hundredth of initial levels and remove toxic-metal catalysts from their process, just using enzymes to synthesize the pharmaceuticals.

I am also excited about reducing the cost and time necessary to develop these enzymes and the processes they are used in. I am working to incorporate machine learning [ML] and artificial intelligence [AI] into this evolutionary optimization. It promises to allow us to develop biological solutions much faster than in the past.

Everything that nature does is efficient. Its this highly evolved system that makes and breaks chemical bonds, creating chemicals and materials of magnificent functionality but that wont persist forever. I think that biological chemistry, with its very high selectivity and power efficiency, can broaden our thinking around fabrication and recycling. Not only can we help break down everything we use in our daily lives into recyclable elements, we can also help create new products entirely, things which are not possible using traditional chemistry.

Biological chemistry can have a beneficial effect on any application of conventional chemistry, and we should use it to find efficiencies. Life today is the product of 4 billion years of evolution, not of engineers in a laboratory. Nature has a lot to teach us.

We founded Gevo [Green Evolution] in 2004 to make fuels from renewable resources. The concept was to engineer enzymes in yeast to make isobutanol, a precursor to jet fuel, instead of ethanol. Today, Gevo is one of the leaders in the development of renewable aviation fuel.

The second company, Provivi, was founded in 2014 to replace toxic pesticides. We developed processes to make non-toxic pheromones, chemicals that serve as signaling mechanisms, which, when sprayed in the field, confuse the mating instinct of insects. Our focus is to create a new foundation for safer, affordable, and sustainable crop protection.

The third company, Aralez Bio, was formed more recently, in 2019. It uses enzymes to make pharmaceutical intermediates.1 They can make hundreds of new amino acids and other chemical building blocks, while cutting waste, energy consumption, and costs.

Evolution is a process. Its turning the crank of mutation and artificial selection. We can harness the power of evolution by automating and empowering it, using AI and ML. I have been publishing on this for 10 years. But even more exciting is that some of these generative AI capabilities are being used to invent proteins from scratch. Enzymes are more complicated, but I predict it will be possible to invent them, too, in the future. This is the convergence of experimental capabilities, understanding the features that really make up a successful protein and then harnessing the new methodologies made available through generative AI.

I predict that, in the next few years, AI is going to be a powerful force one capable of recoding life.

I am on the board of Generate Biomedicines, a biotech startup, which uses AI to generate therapeutic proteins that could be used to cure diseases. Machine learning algorithms can generate novel sequences for proteins that have never been seen in nature. These algorithms analyze hundreds of millions of known proteins, looking for statistical patterns linking amino acid sequence, structure, and function. Using these learned statistical patterns, the company generates custom protein therapeutics from short peptides to complex antibodies, enzymes, gene therapies, and yet-to-be-described protein compositions.

Try different things. I tried many fields of science before I found what I love to do. If youre going to change the world, youve got to be fearless. Dont feel that you have to stick with something just because you said you were going to do it. If you dont like it, do something else.

It has to be both. What we have learned during the pandemic is, you can have all the science and technology you want, but if people wont be vaccinated, it doesnt do any good at all. We can offer scientific solutions, good or bad, but if people dont want them and dont accept the necessary behavioral changes, its not going to happen. So, this interface between science and people is vitally important.

I would love to see respect for biodiversity. I would love to see respect for the natural world that we rely on, but that we treat so badly. I would love to see the natural world being accounted for as an invaluable asset on which our very existence depends.

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Discussion with Frances Arnold | Research & insight - Capgemini

RYAN ANDERSON/Stuff

A digital, 3D simulation of a lung which can simulate different medical problems

In the not-too-distant future, an entirely digital version of you could test whether medical procedures or drugs will work while your real body is untouched.

It sounds like an episode of dark sci-fi show Black Mirror, but reality is catching up.

The Auckland Bioengineering Institute has been working for more than 20 years on creating digital twins of people accurate right down to the atom in order to improve medical and physiological treatment.

The idea is that, by having a digital version of yourself, not only will medical professionals have a better idea of the symptoms you have to begin with, they can also test how a treatment would affect your body.

READ MORE:* Alimetry: The Auckland startup that wants to digitise your gut* Vaping could cause new lung disease 'epidemic', researchers warn* Subtitle technology for hearing impaired trialled at NZ cinema

For example, your digital self could be given a medical drug to see how its going to help you and what any side effects might be, said ABI deputy director professor Merryn Tawhai.

Along with other innovations researchers are working on, the concept is on display at The Cloud in Auckland as part of a showcase by the ABI.

RYAN ANDERSON/Stuff

A belt that can be used at home is able to send tiny signals into the body, to let people with chronic lung problems know if theyre okay

Its something we have been working on for the past 30 years, Tawhai said.

It can represent your clinical data but it also allows us to create virtual cohorts for clinical trials.

Tests can be done on specific age groups or pathology types in a faster timeframe and with no risk to people, she said.

Tawhai did note that there would still need to be discussions about how to safe keep your digital clone and who would have access to it.

The showcase also allows researchers to help inspire the next generation, she said.

There are a lot of very bright people who go into medicine, but could easily have gone into engineering and biomedical engineering and ended up influencing thousands of lives.

RYAN ANDERSON/Stuff

Dr Joyce John, left, shows the effects of vaping on the lungs.

One invention on display is a belt attached to a series of sensors, which could be used at home by people with chronic lung problems to detect whether they have any problems needing medical attention.

The belt sends tiny signals into the body, which the electrical impedance tomography device uses to feed back data on how much fluid is in the lungs.

A gadget like that usually costs more than $50,000 in the US.

Tawhai said that although there isnt a price for the device yet, as theres still a little work to be done on it, but it currently costs $200 to make one with that figure expected to drop.

The device could help people with potential heart failure or chronic asthma, she said.

Other tech on display includes a needle-free injection, which shoots out a liquid drug at a speed fast enough to break through the skin.

Post-doctoral fellow Dr Joyce John said one part of the research the lung team was looking at was replicating how particles move through a persons airways when theyre vaping.

It will help researchers model and simulate the long-term effects of vaping, which is still a relatively new activity, she said.

The Auckland Bioengineering Institute showcase runs until May 14 at The Cloud in Aucklands Viaduct.

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Scientists create digital doppelgangers to test drugs on your behalf - Stuff