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== Applications == {{see also|mRNA vaccine|RNA therapeutics}} The administration of a [[nucleoside-modified messenger RNA]] sequence can cause a cell to make a protein, which in turn could directly treat a disease or could function as a [[vaccine]]; more indirectly the protein could drive an endogenous [[stem cell]] to differentiate in a desired way.<ref name=NatRevMat>{{cite journal| vauthors = Hajj KA, Whitehead KA |title=Tools for translation: non-viral materials for therapeutic mRNA delivery|journal=Nature Reviews Materials|date=12 September 2017|volume=2|issue=10|pages=17056|doi=10.1038/natrevmats.2017.56|bibcode=2017NatRM...217056H|doi-access=free}}</ref><ref name="GEN">{{cite news| vauthors = Gousseinov E, Kozlov M, Scanlan C |title=RNA-Based Therapeutics and Vaccines|url=https://www.genengnews.com/gen-exclusives/rna-based-therapeutics-and-vaccines/77900520|work=Genetic Engineering News|date=September 15, 2015}}</ref> The primary challenges of RNA therapy center on delivering the RNA to the appropriate cells.<ref name="genemed">{{cite journal|vauthors=Kaczmarek JC, Kowalski PS, Anderson DG|date=June 2017|title=Advances in the delivery of RNA therapeutics: from concept to clinical reality|journal=Genome Medicine|volume=9|issue=1|pages=60|doi=10.1186/s13073-017-0450-0|pmc=5485616|pmid=28655327 |doi-access=free }}</ref> Challenges include the fact that naked RNA sequences naturally degrade after preparation; they may trigger the body's [[immune system]] to attack them as an invader; and they are [[Semipermeable membrane|impermeable]] to the [[cell membrane]].<ref name="GEN"/> Once within the cell, they must then leave the cell's transport mechanism to take action within the [[cytoplasm]], which houses the necessary [[ribosomes]].<ref name=NatRevMat/> Overcoming these challenges, mRNA as a therapeutic was first put forward in 1989 "after the development of a broadly applicable in vitro transfection technique."<ref>{{cite journal | vauthors = Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ | title = Developing mRNA-vaccine technologies | journal = RNA Biology | volume = 9 | issue = 11 | pages = 1319–30 | date = November 2012 | pmid = 23064118 | pmc = 3597572 | doi = 10.4161/rna.22269 }}</ref> 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 gene editing|CRISPR]] may also benefit from using mRNA to induce cells to make the desired [[Cas9|Cas]] protein.<ref>{{Cite web| vauthors = Haridi R |date=2021-04-23|title=The mRNA revolution: How COVID-19 hit fast-forward on an experimental technology|url=https://newatlas.com/science/mrna-revolution-vaccine-covid-therapy-pandemic-future-cancer/|access-date=2021-04-26|website=New Atlas|language=en-US}}</ref> Since the 2010s, RNA vaccines and other RNA therapeutics have been considered to be "a new class of drugs".<ref>{{Citation|title=mRNA-based therapeutics–developing a new class of drugs.|date=2014|work=[[Nature Reviews Drug Discovery]]|volume=13|issue=10|pages=759–780|language=en|pmid=25150148|vauthors=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 |doi=10.1093/nar/gku757 |doi-access=free |pmc=4176373}}</ref> The first mRNA-based vaccines received restricted authorization and were rolled out across the world during the [[COVID-19 pandemic]] by [[Pfizer–BioNTech COVID-19 vaccine]] and [[Moderna COVID-19 vaccine|Moderna]], for example.<ref name="pmid35534554">{{cite journal | vauthors = Barbier AJ, Jiang AY, Zhang P, Wooster R, Anderson DG | title = The clinical progress of mRNA vaccines and immunotherapies | journal = Nature Biotechnology | volume = 40 | issue = 6 | pages = 840–854 | date = June 2022 | pmid = 35534554 | doi = 10.1038/s41587-022-01294-2 | s2cid = 248667843 | doi-access = free }}</ref> The 2023 [[Nobel Prize in Physiology or Medicine]] was awarded to [[Katalin Karikó]] and [[Drew Weissman]] for the development of effective mRNA vaccines against COVID-19.<ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 2023 |url=https://www.nobelprize.org/prizes/medicine/2023/press-release/ |access-date=2023-10-03 |website=NobelPrize.org |language=en-US}}</ref><ref>{{Cite news |date=2023-10-02 |title=Hungarian and US scientists win Nobel for COVID-19 vaccine discoveries |language=en |work=Reuters |url=https://www.reuters.com/article/nobel-prize-medicine-idCAKCN3120KJ |access-date=2023-10-03}}</ref><ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 2023 |url=https://www.nobelprize.org/prizes/medicine/2023/kariko/facts/ |access-date=2023-10-03 |website=NobelPrize.org |language=en-US}}</ref>
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