In early January this year, Chinese authorities shared the genetic sequence of SARS-CoV-2, the novel coronavirus.1 With this information, researchers identified the sequence for the spike protein, a key protein found on the surface of the virus. The spike protein showed the potential to be a viable vaccine candidate and formed the basis for messenger RNA (mRNA) vaccine development for COVID-19.
mRNA vaccines platforms are one of the most promising technologies harnessed to develop a COVID-19 vaccine. Moderna, which specializes in mRNA therapeutics, became the first company to test a vaccine against the novel coronavirus in humans. Moderna’s mRNA vaccine candidate has entered phase two of clinical trials, representing an important milestone in bringing the vaccine closer to the markets.
How do mRNA Vaccines Work?
mRNA vaccine platforms work on a fascinating concept - in these platforms, an in vitro transcribed (IVT) mRNA sequence that encodes a disease-specific antigen is introduced into the cell. Once inside the cell, the mRNA is translated into the target protein, in this case, the antigen, to trigger the body’s immune system. The IVT mRNA is engineered to resemble a fully processed mature mRNA molecule as they occur naturally. Thanks to advances in technology, the mRNA can be engineered to be more stable and highly translatable through various modifications. As the final step, IVT mRNA is degraded by normal physiological processes, reducing the risk of metabolite toxicity.2
The History of mRNA Vaccines - Initial Findings Were Met With Skepticism
The effectiveness of mRNA vaccines for direct gene transfer was first reported by Woff et al. in 1990. Woff and colleagues demonstrated that “naked DNA,” that is, plasmid DNA formulated without transfecting agents, could be directly injected into mouse muscle with resultant expression of the encoded protein by cells. The researchers demonstrated that naked RNA could similarly result in the in vivo expression of encoded protein; however, more attention focused on utilizing plasmid DNA, rather than mRNA, likely because of concerns about the instability of mRNA.3
In 1992, a study by Bloom et al. demonstrated that the administration of vasopressin-encoding mRNA in the hypothalamus could elicit a physiological response in rats. In 1993, liposome-formulated mRNA was shown to generate influenza-specific cytolytic T cells in mice. However, due to the potential concerns with mRNA instability, high innate immunogenicity, and inefficient in vivo delivery, these early promising results did not lead to substantial investment in mRNA therapeutics, and more emphasis was laid on DNA-based and protein-based therapeutics.4,5
Two Major Developments Changed the Perception towards mRNA
Though many mRNA studies showed promising results, much emphasis was on DNA based technologies, which explained the difference in excitement about the technologies. However, two developments changed the perception and reality of mRNA. In 2005, Weissman and Kariko found that modified nucleosides made IVT mRNA less immunogenic. In a follow-up study, they showed that using pseudouridine instead of uridine resulted in mRNA that was more stable and had increased translational capacity. The use of modified nucleosides thus addressed critical issues for mRNA—stability of the mRNA, increased production of the encoded protein, and some decrease of the innate immunogenicity.6,7
What Makes mRNA Vaccines an Attractive Option for COVID-19?
The ability to make an mRNA construct by merely knowing the genetic sequence of the desired antigen makes mRNA a relatively faster technology to produce a vaccine for a pandemic like COVID-19.
And if you are looking for mRNA Vaccines or other medical devices and supplies, then PharmaSources could help you. Apart from ...
(All Rights Reserved)