via University of Pittsburgh School of Medicine
Cheap, Potent Pathway to Pandemic Therapeutics
By capitalizing on a convergence of chemical, biological and artificial intelligence advances, University of Pittsburgh School of Medicine scientists have developed an unusually fast and efficient method for discovering tiny antibody fragments with big potential for development into therapeutics against deadly diseases.
The technique, published today in the journal Cell Systems, is the same process the Pitt team used to extract tiny SARS-CoV-2 antibody fragments from llamas, which could become an inhalable COVID-19 treatment for humans. This approach has the potential to quickly identify multiple potent nanobodies that target different parts of a pathogen—thwarting variants.
“Most of the vaccines and treatments against SARS-CoV-2 target the spike protein, but if that part of the virus mutates, which we know it is, those vaccines and treatments may be less effective,” said senior author Yi Shi, Ph.D., assistant professor of cell biology at Pitt. “Our approach is an efficient way to develop therapeutic cocktails consisting of multiple nanobodies that can launch a multipronged attack to neutralize the pathogen.”
Shi and his team specialize in finding nanobodies—which are small, highly specific fragments of antibodies produced by llamas and other camelids. Nanobodies are particularly attractive for development into therapeutics because they are easy to produce and bioengineer. In addition, they feature high stability and solubility, and can be aerosolized and inhaled, rather than administered through intravenous infusion, like traditional antibodies.
By immunizing a llama with a piece of a pathogen, the animal’s immune system produces a plethora of mature nanobodies in about two months. Then it’s a matter of teasing out which nanobodies are best at neutralizing the pathogen—and most promising for development into therapies for humans.
That’s where Shi’s “high-throughput proteomics strategy” comes into play.
“Using this new technique, in a matter of days we’re typically able to identify tens of thousands of distinct, highly potent nanobodies from the immunized llama serum and survey them for certain characteristics, such as where they bind to the pathogen,” Shi said. “Prior to this approach, it has been extremely challenging to identify high-affinity nanobodies.”
After drawing a llama blood sample rich in mature nanobodies, the researchers isolate those nanobodies that bind specifically to the target of interest on the pathogen. The nanobodies are then broken down to release small “fingerprint” peptides that are unique to each nanobody. These fingerprint peptides are placed into a mass spectrometer, which is a machine that measures their mass. By knowing their mass, the scientists can figure out their amino acid sequence—the protein building blocks that determine the nanobody’s structure. Then, from the amino acids, the researchers can work backward to DNA—the directions for building more nanobodies.
Simultaneously, the amino acid sequence is uploaded to a computer outfitted with artificial intelligence software. By rapidly sifting through mountains of data, the program “learns” which nanobodies bind the tightest to the pathogen and where on the pathogen they bind. In the case of most of the currently available COVID-19 therapeutics, this is the spike protein, but recently it has become clear that some sites on the spike are prone to mutations that change its shape and allow for antibody “escape.” Shi’s approach can select for binding sites on the spike that are evolutionarily stable, and therefore less likely to allow new variants to slip past.
Finally, the directions for building the most potent and diverse nanobodies can then be fed into vats of bacterial cells, which act as mini factories, churning out orders of magnitude more nanobodies compared to the human cells required to produce traditional antibodies. Bacterial cells double in 10 minutes, effectively doubling the nanobodies with them, whereas human cells take 24 hours to do the same.
“This drastically reduces the cost of producing these therapeutics,” said Shi.
Shi and his team believe their technology could be beneficial for more than just developing therapeutics against COVID-19—or even the next pandemic.
“The possible uses of highly potent and specific nanobodies that can be identified quickly and inexpensively are tremendous,” said Shi. “We’re exploring their use in treating cancer and neurodegenerative diseases. Our technique could even be used in personalized medicine, developing specific treatments for mutated superbugs for which every other antibiotic has failed.”
Original Article: Cheap, Potent Pathway to Pandemic Therapeutics
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
- Research links red meat intake, gut microbiome, and cardiovascular disease in older adults
A new study shows older adults who ate about a serving of meat daily had a 22 percent higher risk of cardiovascular disease than those who didn’t eat meat, and identifies biologic pathways that help ...
- Heart Disease Will Surge Over the Coming Decades
The prevalence of cardiovascular (CV) risk factors and disease is projected to fall in white individuals by 2060 and increase in all other races and ethnicities. For example, among Black adults, the ...
- DiaMedica Therapeutics to Participate in the BTIG Biotechnology Conference 2022
DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage biopharmaceutical company focused on developing novel treatments for neurological disorders and kidney diseases, today announced that the ...
- Why Beam Therapeutics Stock Dipped Today
Beam Therapeutics stock is under pressure today following a clinical hold on its lead blood cancer candidate. The company didn't go into the specifics behind the clinical hold in its press release.
- 8 health issues that worsened during the pandemic
Increased isolation, missed screenings and disrupted public health activities have caused many of the nation's most pressing health issues to worsen since 2020. Here are eight such issues: 1. Heart ...
Go deeper with Google Headlines on:
Go deeper with Bing News on:
- Scientists design two-in-one antibodies against COVID-19 variants
Chinese scientists and their US counterparts have developed two cocktail antibodies against COVID-19 that may deliver a one-two pu ...
- Phage therapeutics can be used to fight multidrug-resistant pathogens
Scientists with the Texas A&M College of Agriculture and Life Sciences were among those providing the biochemical tools needed to help save a man's life through a unique emergency intervention in 2016 ...
- Efficacy of monoclonal antibodies against Omicron BA.1, BA.2, and BA.5
Currently used therapeutic mAbs that neutralize the BA ... (AZD8895), and Evusheld (AZD7442), the latter of which is a cocktail of tixagevimab and cilgavimab. A standardized assay based on the ...
- Managing phage therapy to help save lives
Their study, “Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages ... use of well-characterized phages in a phage cocktail can avoid redundancy and significantly ...
- Are We Getting Closer to a Potential Universal Coronavirus Monoclonal Therapeutic?
One key aspect of the current research study was finding an antibody target on a part of the spike called the S2, or the stalk region, which is highly conserved.
Go deeper with Google Headlines on: