Coronavirus-like nanoparticles could be a positive control for COVID-19 testing

Rapid COVID-19 tests are on the rise to deliver results faster to more people, and scientists need an easy, silly way to know that these tests are working properly and can be trusted. results. Discoverable nanoparticles such as the novel coronavirus may be just the ticket.

Such nanoparticles would resemble a coronavirus, developed by nanoengineers at the University of California San Diego, as something called advanced control for COVID-19 tests. Positive controls are the samples that will always be positive. They are properly run and monitored along with patient samples to confirm that COVID-19 tests are working consistently and as expected.

The advanced controls developed at UC San Diego offer several advantages over those currently used in the COVID-19 test: no need to keep them cold; they are easy to make; they can be incorporated into the whole testing process from start to finish, just like a patient sample; and because they are not true virus samples from COVID-19 patients, they do not pose a risk of infection to the people running the tests.

Researchers led by Nicole Steinmetz, professor of nanoengineering at UC San Diego, published their work in the journal Biomacromolecules.

This work builds on an earlier version of the advanced controls developed by the Steinmetz laboratory for the RT-PCR test, which is the gold standard for the COVID-19 test. The advanced controls in the new study can be used not only for the RT-PCR test, but also for a cheaper, simpler and faster test called the RT-LAMP test, which can be done on the spot and give results passed in about an hour.

There is a hard tool to ensure that these tests are running properly-; specifically for technical diagnostic assessments such as the RT-LAMP-; crucial, Steinmetz said. It could help enable rapid rapid testing of COVID-19 in areas with low facilities, protected areas and other places that do not have access to solemn testing equipment, specialized feedback and trained professionals.

Advanced controls updated

The new advanced controls are largely tiny virus shells — produced by a plant virus or bacteriophage —; that house keeps sections of coronavirus RNA inside. The RNA segments contain binding sites for both of the primers used in the PCR and LAMP experiments.

“This design creates an all-in-one control that can be used for one of these assessments, making it highly multifunctional,” said former author Soo Khim Chan, who is a postgraduate research in the Steinmetz laboratory.

The team developed two types of progressive control. One was made from plant virus nanoparticles. To make them, the researchers caught cowpea plants in the laboratory with cowpea chlorotic mottle virus and then extracted the viruses from the plants. Subsequently, the researchers removed the RNA virus and inserted an RNA template specifically containing specific but non-infectious strains of the SARS-CoV-2 virus. The nanoparticles are the result of coronavirus RNA sequences packaged inside the shells of plant viruses.

The other advanced control was performed from bacteriophage nanoparticles. There was a similar recipe. The infectious researchers E. coli bacteria with specially-made plasmids; rings of DNA-; containing specific fragments of sequences (which are also non-infectious) from the SARS-CoV-2 virus, as well as gene coding for bacteriophage surface proteins called Qbeta. This process caused the bacteria to form nanoparticles made up of coronavirus RNA sequences packed inside bacteriophage shells.

Plant viruses and bacteriophage shells are essential in making these advanced controls so robust. They protect the coronavirus RNA pieces from breaking down at warmer temperatures-; tests have shown that they can be stored for a week at temperatures up to 40 C (104 F). The shells also protect the RNA during the first phase of the PCR and LAMP tests, which involve the breakdown of cells in the sample-; tro enzyman no teas-; to release their genetic material for testing.

These protections are not present in the advanced controls currently used in the COVID-19 test (naked synthetic RNAs, plasmids or RNA samples from infected patients). This is why the existing controls need to be cooled (which makes them inconvenient to handle, costly to remove and store) or must be added at a later stage of the test (i.e. means that scientists will not know if something went wrong in the early stages).

As a next step, the researchers are looking to partner with industry to implement this technology. The advanced controls can be converted to any RT-PCR or RT-LAMP based assay, and would help to ignore false readings, the Steinmetz team said. Moreover, these advanced controls can be largely achieved by molecular farming in plants or microbial culture fermentation, which is good news for their translation into large-scale production.

“With mutants and mutations emerging, continuous testing will be critical to keeping the population safe,” Steinmetz said. “The new technology could find convenience specifically for home testing, which may lead to a higher rate of false readings due to the uncontrolled experimental conditions.”