Difference between revisions of "Timeline of mRNA research"
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| 2010 || || || "Derrick Rossi, working at Harvard Medical School, built upon Shinya Yamanaka’s work of inducing pluripotency and used RNA to create embryonic stem cells from adult cells (Warren et al., 2010). This eventually led to the foundation of Moderna in 2010. "<ref name="The DNA Unive"/> | | 2010 || || || "Derrick Rossi, working at Harvard Medical School, built upon Shinya Yamanaka’s work of inducing pluripotency and used RNA to create embryonic stem cells from adult cells (Warren et al., 2010). This eventually led to the foundation of Moderna in 2010. "<ref name="The DNA Unive"/> | ||
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| + | | 2014 || || || "Applications of mRNA technology. During the following years, various pre-clinical and clinical trials on mRNA-based vaccines against infectious diseases, hypersensitivities and cancer were completed (Sahin et al., 2014; Weissman, 2015)."<ref name="The DNA Unive"/> | ||
| + | |- | ||
| + | | 2015 || || || "Applications of mRNA technology. During the following years, various pre-clinical and clinical trials on mRNA-based vaccines against infectious diseases, hypersensitivities and cancer were completed (Sahin et al., 2014; Weissman, 2015)."<ref name="The DNA Unive"/> | ||
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| 2015 || || || "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. Karikó and Weissman modified the RNA by inserting a naturally occurring modified nucleoside: pseudouridine."<ref name="The DNA Unive"/> | | 2015 || || || "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. Karikó and Weissman modified the RNA by inserting a naturally occurring modified nucleoside: pseudouridine."<ref name="The DNA Unive"/> | ||
Revision as of 21:09, 11 March 2022
This is a timeline of mRNA research. Today, mRNA is a widely recognized and potent tool for generating antigen-specific immunity in the field of vaccines and immunotherapy.[1]
Contents
Sample questions
The following are some interesting questions that can be answered by reading this timeline:
Big picture
| Time period | Development summary | More details |
|---|---|---|
| 1961–1989 | Early research | ": It started in 1961, when Brenner and colleagues described the presence of an unstable intermediate molecule that copies the information encoded by the DNA and directs the synthesis of proteins: RNA." |
| 1990 onwards | The rise: mRNA as a therapeutic agent | "In the 1990s, mRNA vaccines for personalized cancer have been developed, relying on non-nucleoside modified mRNA. mRNA based therapies continue to be investigated as a method of treatment or therapy for both cancer as well as auto-immune, metabolic, and respiratory inflammatory diseases. Gene editing therapies such as CRISPR may also benefit from using mRNA to induce cells to make the desired Cas protein."[2][3] |
| 2001–2020 | Development | "Since the 2010s, RNA vaccines and other RNA therapeutics have been considered to be "a new class of drugs.""[4] |
| 2020 onwards | Acceleration |
Full timeline
| Year | Month and date | Event type | Details |
|---|---|---|---|
| 1909 | "In 1909, Paul Ehrlich suggested that the immune system may suppress tumor development. Today his prediction is coming true—one of the most exciting and promising applications for synthetic mRNA is immunotherapy for cancer. Because of its great potential, this field has attracted many talented researchers and led to many scholarly publications."[1] | ||
| 1950 | "In 1950, it was first hypothesized that RNA was synthesized in the nucleus and then transferred into the cytoplasm, where it was aggregating with other molecules (Jeener and Szafarz 1950)"[5] | ||
| 1953 | "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?"[3] | ||
| 1960 | The idea of mRNA is first conceived by Sydney Brenner and Francis Crick on 15 April 1960 at King's College, Cambridge, while François Jacob tells them about a recent experiment conducted by Arthur Pardee, himself, and Jacques Monod.[6] | ||
| 1961 | "A better appreciation of the role of RNA was gained in 1961 when three publications revolutionized the way gene function was perceived by establishing messenger RNA (mRNA) as an information carrier in a transitional stage towards the synthesis of protein (Brenner et al. 1961; Gros et al. 1961; Jacob and Monod 1961)"[5] "Discovery of mRNA: It started in 1961, when Brenner and colleagues described the presence of an unstable intermediate molecule that copies the information encoded by the DNA and directs the synthesis of proteins: RNA. The group around Brenner worked with virus-infected cells and analysed the gene expression. They concluded that the protein-encoding information is not present in stable ribosomal RNA. Instead, a transient RNA molecule acts as a transcript of the genetic code. This RNA was termed messenger RNA (mRNA). Ribosomes synthesise proteins according to the information dictated by mRNA (Brenner et al., 1961)."[3] | ||
| 1963 | "Nucleic acids can induce interferon production: In 1963, Isaacs et al. demonstrated that viral nucleic acids can induce the production of interferon in infected chick, rabbit, and mouse cells. The production of interferon supports the fact that nucleic acid is considered foreign to the cell (Isaacs et al., 1963)."[3] | ||
| 1969 | "In-vitro mRNA translation: In 1969, mRNA was translated in the lab for the first time. Lockard and Lingrel, who worked together at the University of Cincinnati, Ohio, provided the first evidence of in-vitro translation of mRNA. They used a mammalian (rabbit) cell-free system to demonstrate the translation of an mRNA transcript from another mammalian species (Lockard and Lingrel, 1969)."[3] | ||
| 1978 | "Liposomes as mRNA delivery vehicle: In 1978, liposomes were utilised for the delivery of mRNA to eukaryotic cells (Dimitriadis, 1978). By the end of the following decade, a cationic liposome mRNA delivery system, DOTMA, was described and commercialised (Malone et al., 1989)."[3] | ||
| 1983 | "It was not until the mid-1980s that the first elements of the answer were identified when it was reported that the actin mRNA in ascidian oocytes and embryos was asymmetrically distrib�uted (Jeffery et al. 1983)"[5] | ||
| 1984 | "SP6 and T7 RNA polymerase: Moreover, in 1984, experimental work showed that any desired cDNA can be utilised for the synthesis of functional mRNAs and, consequently, the synthesis of proteins (Krieg and Melton, 1984). In light of this work, SP6 RNA polymerase was eventually commercialised. In addition to SP6 polymerase, researchers extracted and purified T7 RNA polymerase. In 1985, they also designed a T7 polymerase-promoter complex for the controlled expression of specific genes that is still used today (in upgraded form) (Tabor & Richardson, 1985). These pioneer experiments lead to an unstoppable series of practical work concerning mRNA delivery and commercialisation."[3] | ||
| 1985 | "SP6 and T7 RNA polymerase: Moreover, in 1984, experimental work showed that any desired cDNA can be utilised for the synthesis of functional mRNAs and, consequently, the synthesis of proteins (Krieg and Melton, 1984). In light of this work, SP6 RNA polymerase was eventually commercialised. In addition to SP6 polymerase, researchers extracted and purified T7 RNA polymerase. In 1985, they also designed a T7 polymerase-promoter complex for the controlled expression of specific genes that is still used today (in upgraded form) (Tabor & Richardson, 1985). These pioneer experiments lead to an unstoppable series of practical work concerning mRNA delivery and commercialisation."[3] | ||
| 1988 | "Dr. Robert Malone discovered in-vitro and in-vivo RNA transfection and invented mRNA platform technology while he was at the Salk Institute in 1988. He is thus, the father of the modern mRNA vaccine technology, and he has spoken out against its recent misuse in the COVID-19 pandemic."[7] | ||
| 1989 | mRNA as a therapeutic is first put forward "after the development of a broadly applicable in vitro transfection technique."[8] | ||
| 1989 | "Liposomes as mRNA delivery vehicle: In 1978, liposomes were utilised for the delivery of mRNA to eukaryotic cells (Dimitriadis, 1978). By the end of the following decade, a cationic liposome mRNA delivery system, DOTMA, was described and commercialised (Malone et al., 1989)."[3] | ||
| 1990 | "The use of mRNA as a genetic vector is theoretically attractive because mRNA does not integrate into the genome, is immediately available for translation to make protein, and provides a transient signal, a feature that is desirable for some applications. The demon�stration that mRNA could, in fact, function in this capacity came in 1990, not long after the initial attempts at DNA-based gene ther�apy, when Wolff et al. injected naked mRNA encoding chloram�phenicol acetyl transferase into the skeletal muscle of mice and observed specific protein expression [6]."[1] "The first report of the successful use of in vitro transcribed (IVT) mRNA in animals was published in 1990, when reporter gene mRNAs were injected into mice and protein production was detected"[9][10] | ||
| 1990 | "mRNA expression in-vivo: The foundation of the concept of mRNA as a therapeutic agent was laid by Wolff J. and colleagues in 1990. The team injected naked RNA into mice muscles to provide proof of principle for direct gene transfer in vivo (Wolff et al., 1990)."[3] | ||
| 1991 | "In 1991, mRNA was proposed as an active pharmaceutical ingredient for the treatment of cancer."[11] | ||
| 1992 | "1st use of mRNA as therapeutic molecule: In 1992, a team of scientists working at Scripps Research Institute used mRNA to transiently reverse diabetes insipidus in Brattleboro rats that do not produce the hormone vasopressin (Jirikowski et al., 1992)."[3] | ||
| 1992 | "The use of mRNA as a genetic vector is theoretically attractive because mRNA does not integrate into the genome, is immediately available for translation to make protein, and provides a transient signal, a feature that is desirable for some applications. The demon�stration that mRNA could, in fact, function in this capacity came in 1990, not long after the initial attempts at DNA-based gene ther�apy, when Wolff et al. injected naked mRNA encoding chloram�phenicol acetyl transferase into the skeletal muscle of mice and observed specific protein expression [6]. This was followed in 1992 by a study in which injection of a naked, synthetic mRNA encoding arginine vasopressin into the hypothalami of Brattleboro rats cured the chronic diabetes insipidus suffered by this strain [7]."[1] | ||
| 1992 | "A subsequent study in 1992 demonstrated that administration of vasopressin-encoding mRNA in the hypothalamus could elicit a physiological response in rats"[9][12] | ||
| 1993 | Martinon et al. show that subcutaneous injection of liposome-encapsidated mRNA encoding the influenza virus nucleoprotein induces anti-influenza cytotoxic T lymphocytes.[1] | ||
| 1994 | "In 1994, Kozak postulated that structure in 5′ UTR of mRNAs could act as regulatory sequences to enhance translation by allowing proteins to bind and shift structure downstream"[13] | ||
| 1995 | "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)."[3] | ||
| 1995 | "Improving RNA delivery: In parallel, Pieter Cullis at the University of British Columbia was studying lipids. In 1995, Cullis and his team started working on the application of lipid nanoparticles (liposomes) for the delivery of large biological molecules such as RNA. Even though the system did not work consistently, their work advanced the research on using lipids as an effective and safe delivery system (Bailey & Cullis, 1997)."[3] | ||
| 1997 | Canadian American biologist Jack W. Szostak and Richard W. Roberts show that fusions between a synthetic mRNA and its encoded myc epitope could be enriched from a pool of random sequence mRNA-polypeptide fusions by immunoprecipitation.[14] | ||
| 1997 | "1st mRNA company: All this work in mRNA therapeutics laid the cornerstone of the first mRNA company ever founded: Merix Bioscience (1997). In 2004, the company changed its name to Argos Therapeutics as a sign of its evolution."[3] | ||
| 1997 | "In 1997, the biggest problem encountered by scientists in the process of research was that both natural RNA and artificially synthesized in vitro RNA would activate the response of human immune cells, causing RNA to be degraded before it could be translated into protein.In 1997, the biggest problem encountered by scientists in the process of research was that both natural RNA and artificially synthesized in vitro RNA would activate the response of human immune cells, causing RNA to be degraded before it could be translated into protein."[11] | ||
| 1997 | "In 2007, some scientists conducted research on the application of RNA on stem cells based on the previous method of modifying mRNA uridine, trying to reprogram somatic cells into embryonic stem cells."[11] | ||
| 2008 | "Following the first proposed delivery of self-amplifying RepRNA vaccines by synthetic, biodegradable particles in 2008 [14], complexing the RNA for delivery to DCs has shown applicability for polysaccharide, polyplex and lipoplex. "[15][16] | ||
| 2010 | "Derrick Rossi, working at Harvard Medical School, built upon Shinya Yamanaka’s work of inducing pluripotency and used RNA to create embryonic stem cells from adult cells (Warren et al., 2010). This eventually led to the foundation of Moderna in 2010. "[3] | ||
| 2014 | "Applications of mRNA technology. During the following years, various pre-clinical and clinical trials on mRNA-based vaccines against infectious diseases, hypersensitivities and cancer were completed (Sahin et al., 2014; Weissman, 2015)."[3] | ||
| 2015 | "Applications of mRNA technology. During the following years, various pre-clinical and clinical trials on mRNA-based vaccines against infectious diseases, hypersensitivities and cancer were completed (Sahin et al., 2014; Weissman, 2015)."[3] | ||
| 2015 | "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. Karikó and Weissman modified the RNA by inserting a naturally occurring modified nucleoside: pseudouridine."[3] | ||
| 2018 | "In-vitro transcription of mRNA: Nucleic acids have revolutionised the field of genetics and regenerative medicine. The in-vitro transcription of mRNA has addressed almost all the challenges associated with the use of mRNA as a therapeutic agent. In-vitro transcription is simple, rapid, and controlled. Most importantly, chemical modifications can be introduced to the mRNA strand in-vitro (Kwon et al., 2018)."[3] | ||
| 2020 | December | Pfizer–BioNTech and Moderna obtain authorization for their mRNA-based COVID-19 vaccines. |
Meta information on the timeline
How the timeline was built
The initial version of the timeline was written by User:Sebastian.
Funding information for this timeline is available.
Feedback and comments
Feedback for the timeline can be provided at the following places:
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What the timeline is still missing
Timeline update strategy
See also
External links
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Rhoads, Robert E. (2016). Synthetic MRNA: Production, Introduction Into Cells, and Physiological Consequences. Springer New York. ISBN 978-1-4939-3625-0.
- ↑ "The mRNA revolution: How COVID-19 hit fast-forward on an experimental technology". New Atlas. 23 April 2021. Retrieved 2 March 2022.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 October 29th, reas Ebertz 15 April 2021 (15 April 2021). "The history of mRNA applications". The DNA Universe BLOG. Retrieved 12 March 2022.
- ↑ Kowalska, J; Wypijewska del Nogal, A; Darzynkiewicz, ZM; Buck, J; Nicola, C; Kuhn, AN; Lukaszewicz, M; Zuberek, J; Strenkowska, M; Ziemniak, M; Maciejczyk, M; Bojarska, E; Rhoads, RE; Darzynkiewicz, E; Sahin, U; Jemielity, J (2014). "Synthesis, properties, and biological activity of boranophosphate analogs of the mRNA cap: versatile tools for manipulation of therapeutically relevant cap-dependent processes.". Nucleic acids research. 42 (16): 10245–64. PMID 25150148. doi:10.1093/nar/gku757.
- ↑ 5.0 5.1 5.2 Oeffinger, Marlene; Zenklusen, Daniel (6 December 2019). The Biology of mRNA: Structure and Function. Springer Nature. ISBN 978-3-030-31434-7.
- ↑ Cobb M (29 June 2015). "Who discovered messenger RNA?". Current Biology. 25 (13): R526–R532. PMID 26126273. doi:10.1016/j.cub.2015.05.032
.
- ↑ MD, Justus R. Hope. "Inventor of mRNA banned by the New England Journal of Medicine". The Desert Review. Retrieved 5 March 2022.
- ↑ Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ (November 2012). "Developing mRNA-vaccine technologies". RNA Biology. 9 (11): 1319–30. PMC 3597572. PMID 23064118. doi:10.4161/rna.22269.
- ↑ 9.0 9.1 Pardi, Norbert; Hogan, Michael J.; Porter, Frederick W.; Weissman, Drew (April 2018). "mRNA vaccines — a new era in vaccinology". Nature Reviews Drug Discovery. pp. 261–279. doi:10.1038/nrd.2017.243. Retrieved 5 March 2022.
- ↑ Wolff, Jon A.; Malone, Robert W.; Williams, Phillip; Chong, Wang; Acsadi, Gyula; Jani, Agnes; Felgner, Philip L. (23 March 1990). "Direct Gene Transfer into Mouse Muscle in Vivo". Science. 247 (4949): 1465–1468. doi:10.1126/science.1690918.
- ↑ 11.0 11.1 11.2 Dolgin, Elie (14 September 2021). "The tangled history of mRNA vaccines". Nature. pp. 318–324. doi:10.1038/d41586-021-02483-w. Retrieved 9 March 2022.
- ↑ Jirikowski, Gustav F.; Sanna, Pietro Paolo; Maciejewski-Lenoir, Dominique; Bloom, Floyd E. (21 February 1992). "Reversal of Diabetes Insipidus in Brattleboro Rats: Intrahypothalamic Injection of Vasopressin mRNA". Science. 255 (5047): 996–998. doi:10.1126/science.1546298.
- ↑ 13.0 13.1 Babendure, Jeremy R.; Babendure, Jennie L.; Ding, Jian-Hua; Tsien, Roger Y. (2006-5). "Control of mammalian translation by mRNA structure near caps". RNA. 12 (5): 851–861. ISSN 1355-8382. doi:10.1261/rna.2309906. Check date values in:
|date=(help) - ↑ Roberts RW, Szostak JW (1997). "RNA-peptide fusions for the in vitro selection of peptides and proteins". Proc Natl Acad Sci USA. 94 (23): 12297–302. PMC 24913. PMID 9356443. doi:10.1073/pnas.94.23.12297.
- ↑ Kramps, Thomas; Elbers, Knut (2017). RNA Vaccines: Methods and Protocols. Springer New York. ISBN 978-1-4939-6481-9.
- ↑ Tratschin, Jon Duri; Ruggli, Nicolas; McCullough, Kenneth Charles (10 December 2009). "Pestivirus replicons providing an rna-based viral vector system". Retrieved 5 March 2022.
