Introduction to mRNA May Have Only Just Begun

Ribonucleic acid (RNA) is a single-stranded polymeric (big) molecule that represents itself in living cells in forms such as messenger RNA (mRNA), ribosomal RNA, or transfer RNA.

Unlike the more upstream and nucleus-based role of DNA, RNA plays
a more frontline role across the cell and most directly determines which proteins to build by expression in the cytoplasm and which to tear down (antisense). In broad terms, the DNA plays more the role of the keeper of the recipe, and RNA plays the role of putting the materials together to bake the cake.

Most Sophisticated Medicine Factory Ever Built

The biopharmaceutical manufacturing industry has spent trillions of dollars figuring out how to effectively, and efficiently produce therapeutics, from small molecule oral therapeutics to complex proteins that make up heparins and insulins. Even lithium as a medication requires good manufacturing principles and large investments in instruments, machinery, and production. But what if the human body becomes the principal factory for production? This concept is the basis for all vaccine efficacy: The body reacts to foreign protein and begins to form protective antibodies and countermeasures.

mRNA Vaccines Introduced in 2021

In 2021, the scientific community took the production of therapeutics with- in the human body itself to a new and scalable level. Hundreds of millions of Americans and likely many hundreds of millions more around the world have or will soon receive mRNA vaccines against SARS-CoV-2, which causes the COVID-19 disease. Unlike previous innovations that have produced exogenous proteins that mimic bacteria or viruses to trigger our immune systems to react, mRNA strands already coded to produce the proteins as part of the response in vivo were deployed on a massive scale. Our bodies are the production facilities for these proteins.

Vaccines Prove Exceptionally Effective

As of April 15, just 5800 of nearly 77 million Americans vaccinated against COVID-19 had become infected after receiving the vaccine, and 74 had died. Although the infection rate is likely an underestimation because of vaccinated individuals not regularly testing, deaths are far more likely to be accurately attributed. A quick extrapolation from 74 to approximately 350 million Americans would project roughly 350 “breakthrough” deaths in total across the entire country, and that does not account for the additional protections of herd immunity if everyone is to be vaccinated.

Evolution of Therapeutics Has Brought Targeting

The early days of medicine brought nutraceuticals and therapeutics that came from nature. Then it was a discovery of observation, resulting in opiates and penicillin. Next came the use of animals to create parallel therapeutics in humans for diabetes. A priori hypothesis of small molecules and receptors followed, allowing for better targeting and regulation of core functions and vitals, such as blood pressure to be tested for efficacy and safety. Then came proteins and monoclonal anti- bodies with groundbreaking specificity to targets in the body. Next were stem cells, the promising tissue progenitors but with somewhat unpredictable trajectories. And now the ultimate targeting paired with self-building blocks has arrived. We can produce whatever proteins and therapeutics we like, using our bodies, with nucleotide-level precision.

Agile Development and Expedited Vaccine Production Possible

The production of mRNA and other RNA therapeutics on an assembly line is somewhat universal. Once production facilities are set up, little to no retooling is required to change out codes to respond to variants of infectious disease or the deployment of new codes for other diseases. Imagine the ability to produce a highly effective match at the “code of life” level of precision for an infectious disease or variant and turn that code into an mRNA vaccine for production in the millions of doses in just a few months. It is entirely conceivable that we buttress “guessing” on influenza vaccine types with boosters to match actual breakthrough outbreaks identified in October through December each year for delivery in January through March of the ensuing calendar year. COVID-19 variants? mRNA coded vaccines specific to those variants and their new “spike proteins” are already in development to be tested mere weeks after discovery. If the vehicles for delivery are the same, do we need traditional clinical trials to approve a change in the code to match a variant? Will we continue to “preproduce” and make investments for millions of doses to be ready at the point of FDA application for approvals? These will be the debates and questions that occur this summer.

Vaccines Only Scratch the Surface of Full Capability

It is not just vaccines for infectious disease. RNA has vaulted to the forefront of nucleic acid therapies for nearly every major and many minor disease processes. Cancer, cystic fibrosis, diabetes, and hundreds of other diseases can be treated by giving the “recipe” to our own bodies to produce the needed proteins or tear down the harmful proteins for normally functioning cell and organ processes. Although clustered regularly interspaced short palindromic repeats and gene therapies remain promising, RNA therapeutics give us the ability to target with agility, cost-effective production, and speed like no other scalable technology in biopharmaceutical history and, at least thus far, with an incredible safety profile.

Expanded Use Is Coming Soon

Despite well-known challenges, such as delivery to the targeted cells or organs without degradation or autoimmune responses with therapies needing multiple administrations over time, expect hundreds of RNA- based clinical trials over the next few years. What was once not long ago a few thousand humans using RNA to alleviate disease will soon number in the billions. The genie is out of the bottle. #scienceisawesome

REFERENCE

Edwards E. CDC: about 5800 ‘breakthrough infections’ reported in fully vaccinated people. NBC News. April 15, 2021. Accessed April 28, 2021. https://www.nbcnews. com/health/health-news/cdc-about-5-800-break- through-infections-reported-fully-vaccinated-people-n1264186