Fighting Infections with mRNA

Messenger RNA (mRNA) has proved its mettle. The media are already hinting that it could be useful for more things than Covid-19 vaccines. They aren’t saying any more than that, perhaps because companies such as Pfizer or Moderna are holding their cards close to their vests. But we can make some educated guesses.

It has taken a while to develop the mRNA technology to the point where it could be used to rush the development of essential vaccines. But the basic idea is both simple and straightforward.

Our cells manufacture their own mRNA molecules as copies of genes that can be fed to the cells’ protein-manufacturing machinery (ribosomes), where they tell the machinery what proteins to make and how to make them. The technological version of this takes a mRNA from outside the body (such as the one that says how to make the coronavirus’s spike protein) and injects it into the body. The body’s cells then make the protein. In the Covid-19 case, that means the body’s cells make spike protein and dump it into the bloodstream, where the immune system screams “Enemy!” and gears up to attack the virus.

The logical next question is whether other protein-making instructions (mRNA) can be snuck into our cells in the same way. The answer is, “Yes! Of course!”

The next question is,”Which ones?” To answer, we must consider what kinds of proteins would be useful.

Proteins needed for vaccines? An inevitable choice, considering the likelihood of future viruses and even future pandemics. Existing diseases such as polio, measles, and the like are well covered by traditional (no mRNA) vaccines.

What else? Consider that, because of antibiotic resistance, we are said to be facing the end of the age of antibiotics (https://www.cfr.org/backgrounder/end-antibiotics). We will soon need something to replace them. Fortunately, there is an alternative known as “phage therapy.” Like our own cells, bacterial cells are also attacked by viruses, known as bacteriophages or phages, and each bacterial species is targeted by multiple phages.

A century ago (well before antibiotics were discovered), scientists were working to develop phage therapy. It meant finding phages that could be used to kill bacteria and end infections (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547374/). Once we had antibiotics, interest in phage therapy died down, but now we need it again.

Phages kill bacteria by bursting them. Normally this happens after the phage has multiplied inside the bacterium; bursting releases the next generation of phages. The tool that makes the bursting happen is a protein, a lysin, that digests the bacterial wall.

Intriguingly, a company called Contrafect has a lysin that targets multiply drug-resistant Staphylococcus aureus (MRSA) in Phase III trials. It is also working on others (https://www.contrafect.com/pipeline/overview).  It has received a sizable cash infusion from the Biomedical Advanced Research and Development Authority (BARDA) (https://www.globenewswire.com/news-release/2021/03/11/2191734/0/en/ContraFect-Announces-BARDA-Contract-Award-for-Up-to-86-8-Million-and-Provides-Business-Outlook.html).

It would seem a natural extension of their work to date to develop the mRNAs for the lysins. Injecting that mRNA would tell the body to make a supply of lysin, and Presto! Infection cured. I have not yet seen anything to suggest that they are thinking this way, but I suspect they are. After all, Pfizer (of vaccine fame) has bought more than 600,000 shares of their stock (https://www.globenewswire.com/news-release/2020/05/26/2038529/0/en/ContraFect-Corporation-Announces-Private-Placement-of-Common-Stock-and-Warrants-to-Pfizer-Inc.html).

Are there other bacteria with major drug resistance issues? Tuberculosis comes to mind immediately. A 2007 patent application (http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=2&f=G&l=50&co1=AND&d=PG01&s1=Lysin.AB.&s2=Plyc.AB.&OS=ABST/Lysin+AND+ABST/Plyc&RS=ABST/Lysin+AND+ABST/Plyc) addresses Streptococcus C. According to the Centers for Disease Control, “more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, and more than 35,000 people die as a result.” For a list of worrisome bacteria, see https://www.cdc.gov/drugresistance/biggest-threats.html.

Every one of these bacteria can be attacked via phages and lysins. Indeed, patent applications have already been filed; see e.g. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=44&f=G&l=50&co1=AND&d=PTXT&s1=lysin&s2=bacteria&OS=lysin+AND+bacteria&RS=lysin+AND+bacteria.

And every one of them should be attackable with tailored mRNA injections.

Will we get there? Consider how much Contrafect stock Pfizer has already bought. Are they planning an acquisition?

Further down the road, many diseases result from the lack of a protein in the body due to defective genes. The list includes lipid-storage diseases https://www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/lipid-storage-fact-sheet) and mitochondrial diseases (https://www.umdf.org/what-is-mitochondrial-disease-2/types-of-mitochondrial-disease/). The ideal fix would be a repair to the gene, but gene therapy, though it has been making progress, is still far from being part of the medical toolkit. A short-term way to make the body make missing proteins could well be another application of mRNA technology.

It won’t happen tomorrow. Every new therapy has to go through a long period of development and testing. The mRNA vaccines came fast because the need was urgent. The new applications of the mRNA technology won’t have the same push.

 So. Not tomorrow. But perhaps the day after.

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