Researchers Developing Aerosolized Molecules to Shut Down Production of Destructive SARS-CoV-2 Proteins

Researchers Developing Aerosolized Molecules to Shut Down Production of Destructive SARS-CoV-2 Proteins

A team of researchers at Georgetown University Medical Center have developed molecules containing small strands of RNA which have been shown to shut down the production of the destructive proteins generated by the SARS-CoV-2 virus that cause COVID-19.

MicroRNA (miRNA) and silencing RNA (siRNA) are two types of RNA which interfere with protein production in a virus. By using miRNA or siRNA, it is possible to stop the SARS-CoV-2 virus from producing the proteins which trigger COVID-19, the symptoms of which can be severe and fatal in some individuals.

The GUMC researchers tested several miRNA and siRNA sequences and identified sequences that were effective at suppressing viral protein production by SARS-CoV-2. The researchers have now filed a patent application for the most effective sequences. According to G. Ian Gallicano, PhD, associate professor in the Department Biochemistry and Molecular and Cellular Biology at GUMC, this approach could be effective against virtually any respiratory virus.

The research builds on previous studies conducted by the researchers using miRNA to target genes that affect the ability of the heart to function as a treatment for heart failure. The researchers modified their approach and showed that miRNA and siRNAs can be used to target the messenger RNA used by viruses such as SARS-CoV-2 to generate the proteins necessary for multiplication and infection.

The researchers tested their miRNAs and siRNAs on two types of cells, including human cells from the trachea and demonstrated in the lab that it was possible to suppress protein function in a dose dependent manner, which they confirmed was caused by the degradation of messenger RNA. The researchers found there were fewer off-target effects using siRNAs.

The siRNAs interfere with the protein spikes of the SARS-CoV-2 virus, which are used to gain entry into cells and are a key component of infectivity. By creating an aerosolized siRNA agent, the researchers could ensure that the siRNAs are efficiently delivered where they are needed.

The researchers note that it is possible to make siRNAs fat soluble, which will help them to be absorbed into cells with mucous membranes, such as the cells that line the airways. That makes them suitable for delivery using a nasal spray. Non-soluble fat compounds are not effective using this delivery mechanism as they can cause irritation of the nasal passages.

There are still further experiments needed before the treatment could be considered for clinical use, but the researchers are confident that if the siRNAs prove to be effective, the treatment could be rapidly moved from the lab to a clinical setting.

You can read more about the study in the paper – Molecular targeting of vulnerable RNA sequences in SARS CoV-2: identifying clinical feasibility – which was recently published in the journal Gene Therapy. DOI: 10.1038/s41434-020-00210-0

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