The quick and portable production process, described in a newly accepted paper in the journal New Biotechnology, could be easily deployed at the source of a future virus outbreak
A multidisciplinary research team has produced a promising virus-fighting protein using a quick, portable process that could be easily deployed at the source of a future virus outbreak. The team includes researchers from the University of Maryland, Baltimore County (UMBC), Stanford University, the National Cancer Institute (NCI) and the National Center for Advanced Translational Science. The research has been accepted for publication in the journal New Biotechnology.
Griffithsin is a protein originally isolated from red algae. More than a decade ago, researchers in the Molecular Targets Program of the NCI discovered it could protect cells from the HIV virus and it is now in Phase 1 clinical trials in humans. Griffithsin sticks to the surface glycoproteins of certain viruses, making it difficult for the virus to enter host cells. (Glycoproteins are proteins with sugar molecules on them.)
“It’s like taking clay and sticking it to the prongs of an electrical plug to prevent it from entering a socket,” says Govind Rao, a professor of chemical and biochemical engineering at UMBC who is one of the lead researchers on the project. The protein disables a wide range of viruses, including the virus that causes COVID-19.
Medicines that are made with biological molecules like griffithsin are called biologics. They are normally manufactured in huge batches using living cells such as E.coli bacteria. (The cells are given DNA-encoded instructions for how to make the medicine.) However, that method has drawbacks, including the need to keep the cells alive.
Rao and his colleagues developed a method to manufacture griffithsin that does not require living cells. Instead, the researchers take the protein-manufacturing “guts” out of the cells. Into this soup of cellular components, they then add the DNA instructions for making griffithsin, along with the needed molecular building blocks.
“The cellular machinery still works, even without a living cell to support it,” says Rao. “The method is simple and effective.”
Using cell-free manufacturing methods, the researchers produced significant quantities of griffithsin in less than 24 hours. They purified the protein to strict standards and demonstrated in lab experiments that it could disable both HIV and SARS-CoV-2 virusesas effectively as the same griffithsin protein made by living cells.
The researchers envision that the method could be quickly deployed to make antiviral medicine at the origin of disease outbreaks. The method could be easily adapted to work with a portable, suitcase-sized biologics manufacturing device, dubbed Bio-MOD, that Rao and a team of mostly UMBC researchers recently developed. They described the device in a 2018 paper in the journal Nature Biomedical Engineering.
The new griffithsin protein manufacturing process together with the portable Bio-MOD device could be a powerful weapon to quickly combat new viruses before they spread.
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]]>How To Develop Safe And Effective Medications | Exploring The Next Generation Of Therapeutics
What will the next generation of medicine production look like? Dr. Govind Rao is a Professor of Chemical and Biochemical Engineering, and the Director of the Center for Advanced Sensor Technology at the University of Maryland Baltimore County (UMBC) joins us today to discuss the importance of constructing safe and effective medications – standards that are harder to reach than one may think…
Listen to Govind Rao here: bit.ly/3KdhTr7
Episode also available on Apple Podcasts: apple.co/30PvU9C
By exploring how chemical contaminants move through the environment and affect aquatic food webs, Upal Ghosh, Ph.D., of the University of Maryland, Baltimore County (UMBC), aims to develop and implement technologies to help ecosystems recover from pollution.
With consistent NIEHS funding since 2007, Ghosh studies contaminants called polychlorinated biphenyls (PCBs), which can build up in organisms over time and along the food chain. Ghosh assesses pollutant bioavailability, or the amount of a contaminant available for uptake by fish and other organisms, with a particular focus on PCBs.
“During my undergraduate studies in chemical engineering, I got to visit different industrial sites and understand how we produce chemicals in bulk,” Ghosh said. “Although chemical industries provide many benefits for people — producing thousands of consumer products we use today — I was disappointed to see the problems that occur when chemicals like PCBs are mismanaged and enter the environment.”
His goal is to use nature-based strategies to clean up contaminants and reduce exposures in aquatic organisms and humans alike.
PCBs are a group of chemicals formerly used in many industrial and consumer products, such as electrical equipment, insulation, paint, and plastics. Although the federal government banned PCB production in 1979, the compounds persist in soils, sediments, and water bodies due to their stable chemical structure.
Exposure to PCBs has been associated with a wide variety of health effects, including liver problems, poor birth outcomes, hormone disruption, and cancer. In general, people are exposed to PCBs by eating contaminated fish, meat, or dairy products.
“If we can limit the amount of PCBs bioavailable to fish, we can also help protect human health,” Ghosh explained.
To better understand PCB accumulation in organisms, Ghosh’s team has been studying the Anacostia River in Washington, D.C., which faces ongoing PCB contamination. The river’s long history of urbanization and industrialization has resulted in pollution, poor water quality, and contaminated sediments in the riverbed.
The team deployed passive samplers and freshwater mussels into the Anacostia River as dual methods to identify PCB sources. Mussels are sedentary, long-lived filter feeders that have been shown to accumulate contaminants without metabolizing them. They then developed models to accurately predict PCB accumulation in mussels and different fish species in the river.
According to Ghosh, this research demonstrated that controlling ongoing PCB inputs from one heavily impacted tributary was critical for the reduction of PCB levels in fish.
“At many contaminated sites, we found that PCB hotspots were located near disadvantaged communities, which poses an environmental justice and health equity issue for the people who live there,” Ghosh said.
image credits:
Photo courtesy of Upal Ghosh
Research led by Dr. Govind Rao, Director of Center for Advanced Sensor Technology and professor in the department of Chemical, Biochemical and Environmental Engineering is featured in a recent article posted on leaps.org titled “With This New Technology, Hospitals and Pharmacies Could Make Vaccines and Medicines Onsite, 2023” The story was written based on a preprint of a paper with Shayan Borhani, Chemical Engineering PhD candidate as the first author. Aaron Thole, Chemical Engineering PhD student and Dr. Doug Frey, professor in the department of Chemical, Biochemical and Environmental Engineering are also co-authors. (https://www.biorxiv.org/content/10.1101/2022.12.19.521044v1).
The article describes a process to develop a compelling pandemic mitigation strategy to promptly suppress viral emergence at the source of an outbreak using proteins such as GRFT which are efficacious in neutralizing a broad range of viruses. This process is shown to produce a product with consistent purity and potency in less than 24 hours using cell-free biomanufacturing.
The collaborators demonstrated GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics. Efficacy was demonstrated in vitro against SARS-CoV-2 and HIV-1 and was nearly identical to that of GRFT expressed in vivo. The proposed production process is efficient and can be readily scaled up and deployed anywhere in the world where a viral pathogen might emerge. The current emergence of viral variants has resulted in frequent updating of existing vaccines and loss of efficacy for front-line monoclonal antibody therapies.
Dr. Rao wants to advance technology to the point where any hospital or pharmacy could load up the media containing molecular factories, mix up the necessary amino acids, nucleotides, and enzymes, and harvest the medications in a matter of hours. This will enable on-site and on-demand medication production. Once this approach is thoroughly validated it might revolutionize medicine-making even outside of hospitals and pharmacies and extend beyond urgent situations.
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