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RNA history
RNA company history timeline
In 1953, after Watson and Crick proposed the model of the DNA double helix, a new question arose in the scientific community: how is information encoded by the DNA and how is it translated? The earliest hypothesis of the involvement of RNA came from André Boivin.
In-vitro mRNA translation: In 1969, mRNA was translated in the lab for the first time.
As far back as 1978, scientists had used fatty membrane structures called liposomes to transport mRNA into mouse3 and human4 cells to induce protein expression.
In late 1987, Robert Malone performed a landmark experiment.
If cells could create proteins from mRNA delivered into them, he wrote on 11 January 1988, it might be possible to “treat RNA as a drug”. Another member of the Salk lab signed the notes, too, for posterity.
Both Vical (with the University of Wisconsin) and the Salk began filing for patents in March 1989.
mRNA expression in-vivo: The foundation of the concept of mRNA as a therapeutic agent was laid by Wolff J. and colleagues in 1990.
But the Salk soon abandoned its patent claim, and in 1990, Verma joined Vical’s advisory board.
She and Sahin are physicians who met in 1990 working at a hospital in Saarland.
In 1991, Vical entered into a multimillion-dollar research collaboration and licensing pact with US firm Merck, one of the world’s largest vaccine developers.
Smita Nair, PhD, professor of surgery, came to Duke in 1993 to study cancer therapeutics as a post-doctoral researcher in the lab of Eli Galboa, PhD, now a professor at the University of Miami.
In 1995, Nair and her colleague David Boczkowski made a fortuitous discovery in the lab.
1st use of mRNA as vaccines: Even though the concept of mRNA vaccines sounds relatively advanced, it dates back to 1995, when Robert and his team designed the first mRNA vaccine that encoded cancer antigens (Conry et al., 1995).
By 1995, after six years on the faculty at the University of Pennsylvania, Karikó got demoted.
Nair and Boczkowski published the finding in the Journal of Experimental Medicine in 1996, and the company Argos Technology developed the technology and currently has two products in clinical trials.
Another cancer immunologist had more success, which led to the founding of the first mRNA therapeutics company, in 1997.
In 1997, she began working with Weissman, who had just started a lab at UPenn.
In 2005, the pair reported that rearranging the chemical bonds on one of mRNA’s nucleotides, uridine, to create an analogue called pseudouridine, seemed to stop the body identifying the mRNA as a foe17.
That discovery, described in a series of scientific papers starting in 2005, largely flew under the radar at first, said Weissman, but it offered absolution to the mRNA researchers who had kept the faith during the technology’s lean years.
Derrick Rossi, a native of Toronto who rooted for the Maple Leafs and sported a soul patch, was a 39-year-old postdoctoral fellow in stem cell biology at Stanford University in 2005 when he read the first paper.
Even the Karikó–Weissman patents, licensed to Cellscript and filed in 2006, will expire in the next five years.
They plugged away at the technology for many years, working at Johannes Gutenberg University Mainz in Germany, earning patents, papers and research grants, before pitching a commercial plan to billionaire investors in 2007. “If it works, it will be ground-breaking,” Şahin said.
But Rossi didn’t have vaccines on his mind when he set out to build on their findings in 2007 as a new assistant professor at Harvard Medical School running his own lab.
At just 34, he became CEO of the French diagnostics firm BioMérieux in 2007 but was wooed away to Moderna four years later by Afeyan.
In 2008, for example, both Novartis and Shire established mRNA research units — the former (led by Geall) focused on vaccines, the latter (led by Heartlein) on therapeutics.
In 2009, researchers conducted the first-ever trial on cancer immunotherapy using mRNA-based vaccines in human subjects with metastatic melanoma.
In 2009, after more than a year of work, the postdoc waved Rossi over to a microscope.
In February 2010, it granted exclusive patent rights to a small lab-reagents supplier in Madison.
On a May afternoon in 2010, Rossi and Springer visited Langer at his laboratory in Cambridge.
In 2011, Moderna hired the CEO who would personify its brash approach to the business of biotech.
In 2012, teams led by Jennifer Doudna and Emmanuelle Charpentier independently published papers showing how the power of CRISPR can be harnessed to edit the genome.
After that gene-silencing therapy began to show promise in clinical trials, in 2012, two of Cullis’s companies pivoted to explore opportunities for the LNP delivery system in mRNA-based medicines.
Geall led the first team to combine LNPs with an RNA vaccine22, at Novartis’s US hub in Cambridge in 2012.
BioNTech launched that year, and other start-ups soon entered the fray, bolstered by a 2012 decision by the US Defense Advanced Research Projects Agency to start funding industry researchers to study RNA vaccines and drugs.
In a 2012 Moderna news release, Afeyan said the firm’s “promise rivals that of the earliest biotechnology companies over 30 years ago — adding an entirely new drug category to the pharmaceutical arsenal.”
Moderna made a splash in 2012 with the announcement that it had raised $40 million from venture capitalists despite being years away from testing its science in humans.
In fact, in 2013, the company hired Karikó as senior vice president to help oversee its mRNA work.
In 2013, the firm began disclosing its ambitions to transform the treatment of cancer and soon announced a series of eight partnerships with major drug makers.
“It’s total malarkey,” said Rossi, who ended his affiliation with Moderna in 2014. “I’m embarrassed for them.
In 2015, Katalin Karikó and her colleague Drew Weissmann found the solution to prevent activation of the immune response against the injected mRNA. It has been found that mRNA activates the toll-like receptors (TLR) on immune cells.
Moderna was one of the companies that built on this work and, by 2015, it had raised more than $1 billion on the promise of harnessing mRNA to induce cells in the body to make their own medicines — thereby fixing diseases caused by missing or defective proteins.
Afeyan had the same enthusiastic reaction as Langer, saying in a 2015 article in Nature that Rossi’s innovation “was intriguing instantaneously.”
In 2016, they co-authored an article in the journal science, “From the RNA world to the clinic,” in which they reflected on the rise of RNA editing and vaccine development.
When BioNTech went public last October, it raised $150 million, and closed with a market value of $3.4 billion — less than half of Moderna’s when it went public in 2018.
Most importantly, chemical modifications can be introduced to the mRNA strand in-vitro (Kwon et al., 2018).
The decision to drop the patent application rested with the Salk’s technology-transfer office, he says. (Verma resigned from the Salk in 2018, following allegations of sexual harassment, which he continues to deny.)
Thirdly, as guide RNA and Cas9 mRNA are both single-stranded, they can be encapsulated in a single nanoparticle, ensuring the delivery of both components into the target cells. Therefore, the mRNA platform can address the limitations of gene editing approaches (Xiong et al., 2018).
They reported that the first strong signal of mRNA in the lymphoid node was observed after 4 hours as a result of intramuscular administration (Lindsay et al., 2019).
In March 2020, it partnered with New York-based drug company Pfizer, and clinical trials then moved at a record pace, going from first-in-human testing to emergency approval in less than eight months.
So, why did it take until the global COVID-19 pandemic of 2020 for the first mRNA vaccine to be brought to market?
By the beginning of 2020, Moderna had advanced nine mRNA vaccine candidates for infectious diseases into people for testing.
Global sales of these are expected to top US$50 billion in 2021 alone.
Özlem Türeci (left) and Uğur Şahin (right) co-founded the mRNA vaccine firm BioNTech.Credit: BioNTech SE 2021
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RNA competitors
| Company name | Founded date | Revenue | Employee size | Job openings |
|---|---|---|---|---|
| Cosway | - | $29.0M | 80 | - |
| Gurwitch Products | 1995 | $39.0M | 350 | - |
| HUISH DETERGENTS INC | - | $6.3M | 42 | - |
| Aware Products LA | 1974 | $7.9M | 100 | - |
| 220 Laboratories | - | $50.7M | 150 | - |
| REV Holdings LLC | 1997 | $4.6B | 100 | 45 |
| Neoteric Cosmetics | - | $8.5M | 150 | - |
| LEE Pharmaceuticals | 1971 | $1.6M | 20 | - |
| Temp1 | 1982 | $5.0B | 14,000 | 73 |
| Jamestown | 1983 | $490,000 | 50 | 51 |
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