Vaccine hesitancy in the US has helped to fuel the spread of Covid-19. One of the most common reasons many refuse the vaccine is that they believe it was rushed. This article from Nature spells out the history of the vaccine and shows a timeline of some key milestones for mRNA and lipid nanoparticle development (beginning in 1961) nature.com/articles/s41578-...?
"Messenger RNA (mRNA) has emerged as a new category of therapeutic agent to prevent and treat various diseases. To function in vivo, mRNA requires safe, effective and stable delivery systems that protect the nucleic acid from degradation and that allow cellular uptake and mRNA release. Lipid nanoparticles have successfully entered the clinic for the delivery of mRNA; in particular, lipid nanoparticle–mRNA vaccines are now in clinical use against coronavirus disease 2019 (COVID-19), which marks a milestone for mRNA therapeutics. In this Review, we discuss the design of lipid nanoparticles for mRNA delivery and examine physiological barriers and possible administration routes for lipid nanoparticle–mRNA systems. We then consider key points for the clinical translation of lipid nanoparticle–mRNA formulations, including good manufacturing practice, stability, storage and safety, and highlight preclinical and clinical studies of lipid nanoparticle–mRNA therapeutics for infectious diseases, cancer and genetic disorders. Finally, we give an outlook to future possibilities and remaining challenges for this promising technology."
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neurodervish
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Interesting points Neil. I looked up the average amount of time it takes for a drug to go from development to the market and it appears to be 10 to 15 years. Moderna got US funding in 2010 to help develop an mRNA vaccine for an earlier iteration of the coronavirus—so that was 11 years ago. The current vaccine was expedited in 2020 because researchers in China uploaded the COVID-19 genome sequence to the public.
I am ever mindful that pandemics move quickly, but R&D and government agencies don't always.
Don't forget the explosion in capability resulting from DNA sequencing. We've ever more powerful analysis and editing tools (CRISPR). We've just used the latter for the first ever cure of an inherited condition causing blindness: geneticliteracyproject.org/...
We've experienced a similar previous revolution in microelectronics; transistor theory 1925, practical transistor 1948, silicon wafers 1959, first integrated circuit in 1971 (Intel), followed by doubling computing power every ~18 months (Moore's law) for decades. We've seen from the coronavirus pandemic how rapidly change happens with exponential growth. This time, we are using the exponential growth in computing power to drive the exponential growth in microbiology and genomics.
(The second author, Katalin Karikó laid the scientific groundwork for mRNA vaccines, overcoming major obstacles and skepticism in the scientific community.[1][4] Karikó received the Nobel Prize in Physiology or Medicine in 2023 for her work, along with American immunologist Drew Weissman.[5][6]) - en.m.wikipedia.org/wiki/Kat...
Key Points
- Messenger RNA (mRNA) is a pivotal molecule of life, involved in almost all aspects of cell biology.
- As the subject of basic and applied research for more than 5 decades, mRNA has only recently come into the focus as a potentially powerful drug class able to deliver genetic information.
- Synthetic mRNA can be engineered to resemble mature and processed mRNA molecules as they occur naturally in the cytoplasm of eukaryotic cells and to transiently deliver proteins.
- Recent advances addressed challenges inherent to this drug class and provided the basis for a broad spectrum of applications
- Besides cancer immunotherapies and infectious disease vaccines novel approaches such as in vivo delivery of mRNA to replace or supplement proteins, mRNA-based induction of pluripotent stem cells, or mRNA-assisted delivery of designer nucleases for genome engineering rapidly emerged and entered into pharmaceutical development.
- This Review gives a comprehensive overview of the current state of mRNA drug technologies, their applications and crucial aspects relevant to mRNA based drug discovery and development.
I posted about how an mRNA vaccine has dramatically improved the effectiveness of KEYTRUDA's treatment of stage III/IV melanoma here, healthunlocked.com/user/Aus... where the vaccine has achieved an FDA breakthrough designation as well as the equivalent in Europe.
As the 2014 paper above noted; In the field of therapeutic cancer vaccination, IVT mRNA has undergone extensive preclinical investigation and has reached Phase III clinical testing12,13,14,15,16,17,18.
Exciting times for cancer vaccination breakthroughs! That's particularly welcome news for our community, given our increased risk of secondary primary cancers, even with the new targeted therapies.
Katalin Karikó: The unimaginable, obstacle-laden, multi-decade journey to discover the mRNA platform and win the 2023 Nobel Prize. From her new autobiography BREAKING THROUGH to one of the most important life science breakthroughs of our time, a story that is truly remarkable.
Eric Topol 2nd February 2024
54 minute podcast, recorded 30 January 2023, unedited transcript to follow soon.
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