Editing Small interfering RNA (section)

==History==
In 1998, [[Andrew Fire]] at [[Carnegie Institution for Science]] in Washington DC and [[Craig Mello]] at [[University of Massachusetts]] in Worcester discovered the [[RNA interference|RNAi]] mechanism while working on the gene expression in the nematode, ''[[Caenorhabditis elegans]]''.<ref name = "Eisenstein_2019">{{cite journal | vauthors = Eisenstein M |title=Pharma's roller-coaster relationship with RNA therapies |journal=Nature |date=16 October 2019 |volume=574 |issue=7778 |pages=S4–S6 |doi=10.1038/d41586-019-03069-3 |bibcode=2019Natur.574S...4E |s2cid=204741280 |doi-access= }}</ref> They won the [[Nobel Prize|Nobel prize]] for their research with [[RNA interference|RNAi]] in 2006. siRNAs and their role in post-[[Transcription (genetics)|transcriptional]] [[gene silencing]] (PTGS) was discovered in plants by [[David Baulcombe]]'s group at the [[Sainsbury Laboratory]] in [[Norwich, England|Norwich]], [[England]] and reported in [[Science (journal)|''Science'']] in 1999.<ref>{{cite journal | vauthors = Hamilton AJ, Baulcombe DC | title = A species of small antisense RNA in posttranscriptional gene silencing in plants | journal = Science | volume = 286 | issue = 5441 | pages = 950–2 | date = October 1999 | pmid = 10542148 | doi = 10.1126/science.286.5441.950 | s2cid = 17480249 }}</ref> [[Thomas Tuschl]] and colleagues soon reported in [[Nature (journal)|''Nature'']] that synthetic siRNAs could induce RNAi in mammalian cells.<ref>{{cite journal | vauthors = Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T | title = Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells | journal = Nature | volume = 411 | issue = 6836 | pages = 494–8 | date = May 2001 | pmid = 11373684 | doi = 10.1038/35078107 | s2cid = 710341 | bibcode = 2001Natur.411..494E}}</ref> In 2001, the expression of a specific gene was successfully silenced by introducing chemically synthesized siRNA into mammalian cells (Tuschl et al.) These discoveries led to a surge in interest in harnessing RNAi for [[biomedical research]] and [[drug development]]. Significant developments in siRNA therapies have been made with both organic (carbon based) and inorganic (non-carbon based) [[nanoparticle]]s, which have been successful in [[Nanoparticles for drug delivery to the brain|drug delivery to the brain]], offering promising methods to deliver therapeutics into human subjects. However, human applications of siRNA have had significant limitations to its success. One of these being off-targeting.<ref name="pmid28696921"/> There is also a possibility that these therapies can trigger [[Innate immune system|innate immunity]].<ref name = "Eisenstein_2019" /> Animal models have not been successful in accurately representing the extent of this response in humans. Hence, studying the effects of siRNA therapies has been a challenge.  

In recent years, siRNA therapies have been approved and new methods have been established to overcome these challenges. There are approved therapies available for commercial use and several currently in the pipeline waiting to get approval.<ref>{{Cite journal |last1=Chen |first1=Zhihang |last2=Krishnamachary |first2=Balaji |last3=Pachecho-Torres |first3=Jesus |last4=Penet |first4=Marie-France |last5=Bhujwalla |first5=Zaver M. |date=March 2020 |title=Theranostic small interfering RNA nanoparticles in cancer precision nanomedicine |journal=WIREs Nanomedicine and Nanobiotechnology |language=en |volume=12 |issue=2 |pages=e1595 |doi=10.1002/wnan.1595 |pmid=31642207 |pmc=7360334 |issn=1939-5116}}</ref><ref>{{Cite news|date=10 August 2018|title=New Kind of Drug, Silencing Genes, Gets FDA Approval|work=[[The Wall Street Journal]]|url=https://www.wsj.com/articles/fda-approves-first-drug-based-on-gene-silencing-research-1533923359|access-date=26 March 2021}}</ref>