Editing Prion (section)

=== Sterilization ===
Infectious particles possessing [[nucleic acid]] are dependent upon it to direct their continued replication. Prions, however, are infectious by their effect on normal versions of the protein. Sterilizing prions, therefore, requires the [[denaturation (biochemistry)|denaturation]] of the protein to a state in which the molecule is no longer able to induce the abnormal folding of normal proteins. In general, prions are quite resistant to [[protease]]s, heat, [[ionizing radiation]], and [[formaldehyde]] treatments,<ref>{{cite journal | vauthors = Qin K, O'Donnell M, Zhao RY | title = Doppel: more rival than double to prion | journal = Neuroscience | volume = 141 | issue = 1 | pages = 1–8 | date = August 2006 | pmid = 16781817 | doi = 10.1016/j.neuroscience.2006.04.057 | s2cid = 28822120 }}</ref> although their infectivity can be reduced by such treatments. Effective prion decontamination relies upon protein [[hydrolysis]] or reduction or destruction of [[protein tertiary structure]]. Examples include [[sodium hypochlorite]], [[sodium hydroxide]], and strongly acidic [[detergent]]s such as LpH.<ref>{{cite journal | vauthors = Race RE, Raymond GJ | title = Inactivation of transmissible spongiform encephalopathy (prion) agents by environ LpH | journal = Journal of Virology | volume = 78 | issue = 4 | pages = 2164–5 | date = February 2004 | pmid = 14747583 | pmc = 369477 | doi = 10.1128/JVI.78.4.2164-2165.2004 }}</ref>

The [[World Health Organization]] recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions:

# Immerse in [[Equivalent concentration|1N]]&nbsp;sodium hydroxide and place in a [[Autoclave#Air removal|gravity-displacement autoclave]] at 121&nbsp;°C for 30&nbsp;minutes; clean; rinse in water; and then perform routine sterilization processes.
# Immerse in 1N&nbsp;sodium hypochlorite (20,000&nbsp;parts per million available chlorine) for 1&nbsp;hour; transfer instruments to water; heat in a gravity-displacement autoclave at 121&nbsp;°C for 1&nbsp;hour; clean; and then perform routine sterilization processes.
# Immerse in 1N&nbsp;sodium hydroxide or sodium hypochlorite (20,000&nbsp;parts per million available chlorine) for 1&nbsp;hour; remove and rinse in water, then transfer to an open pan and heat in a gravity-displacement (121&nbsp;°C) or in a porous-load (134&nbsp;°C) autoclave for 1&nbsp;hour; clean; and then perform routine sterilization processes.<ref>{{cite journal | vauthors = Sutton JM, Dickinson J, Walker JT, Raven ND | title = Methods to minimize the risks of Creutzfeldt-Jakob disease transmission by surgical procedures: where to set the standard? | journal = Clinical Infectious Diseases | volume = 43 | issue = 6 | pages = 757–764 | date = September 2006 | pmid = 16912952 | doi = 10.1086/507030 | doi-access = free }}</ref>

{{convert|134|C}} for 18 minutes in a pressurized steam [[autoclave]] has been found to be somewhat effective in deactivating the agent of disease.<ref>{{cite journal | vauthors = Collins SJ, Lawson VA, Masters CL | title = Transmissible spongiform encephalopathies | journal = Lancet | volume = 363 | issue = 9402 | pages = 51–61 | date = January 2004 | pmid = 14723996 | doi = 10.1016/S0140-6736(03)15171-9 | s2cid = 23212525 }}</ref><ref name="pmid10716712">{{cite journal | vauthors = Brown P, Rau EH, Johnson BK, Bacote AE, Gibbs CJ, Gajdusek DC | title = New studies on the heat resistance of hamster-adapted scrapie agent: threshold survival after ashing at 600 degrees C suggests an inorganic template of replication | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 7 | pages = 3418–21 | date = March 2000 | pmid = 10716712 | pmc = 16254 | doi = 10.1073/pnas.050566797 | doi-access = free | bibcode = 2000PNAS...97.3418B }}</ref> [[Ozone]] sterilization has been studied as a potential method for prion denaturation and deactivation.<ref>{{cite web | url=http://www.hpa.org.uk/hpa/news/articles/press_releases/2005/050414_ozone_sterilizer.htm | title=Ozone Sterilization | date=2005-04-14 | publisher=UK Health Protection Agency | access-date=2010-02-28 |archive-url = https://web.archive.org/web/20070210204514/http://www.hpa.org.uk/hpa/news/articles/press_releases/2005/050414_ozone_sterilizer.htm |archive-date=February 10, 2007 }}</ref> Other approaches being developed include [[thiourea]]-[[urea]] treatment, [[guanidinium chloride]] treatment,<ref>{{cite journal | vauthors = Botsios S, Tittman S, Manuelidis L | title = Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms | journal = Virulence | volume = 6 | issue = 8 | pages = 787–801 | date = 2015 | pmid = 26556670 | pmc = 4826107 | doi = 10.1080/21505594.2015.1098804 }}</ref> and special heat-resistant [[subtilisin]] combined with heat and detergent.<ref>{{cite journal | vauthors = Koga Y, Tanaka S, Sakudo A, Tobiume M, Aranishi M, Hirata A, Takano K, Ikuta K, Kanaya S | title = Proteolysis of abnormal prion protein with a thermostable protease from ''Thermococcus kodakarensis'' KOD1 | journal = Applied Microbiology and Biotechnology | volume = 98 | issue = 5 | pages = 2113–20 | date = March 2014 | pmid = 23880875 | doi = 10.1007/s00253-013-5091-7 | s2cid = 2677641 }}</ref> A number of decontamination reagents have been commercially manufactured with significant differences in efficacy among methods.<ref>{{cite journal |last1=Edgeworth |first1=JA |last2=Sicilia |first2=A |last3=Linehan |first3=J |last4=Brandner |first4=S |last5=Jackson |first5=GS |last6=Collinge |first6=J |title=A standardized comparison of commercially available prion decontamination reagents using the Standard Steel-Binding Assay. |journal=The Journal of General Virology |date=March 2011 |volume=92 |issue=Pt 3 |pages=718–26 |doi=10.1099/vir.0.027201-0 |pmid=21084494 |pmc=3081234}}</ref> A method sufficient for sterilizing prions on one material may fail on another.<ref>{{cite journal | vauthors = Eraña H, Pérez-Castro MÁ, García-Martínez S, Charco JM, López-Moreno R, Díaz-Dominguez CM, Barrio T, González-Miranda E, Castilla J | title = A Novel, Reliable and Highly Versatile Method to Evaluate Different Prion Decontamination Procedures | journal = Frontiers in Bioengineering and Biotechnology | volume = 8 | pages = 589182 | date = 2020 | pmid = 33195153 | pmc = 7658626 | doi = 10.3389/fbioe.2020.589182 | doi-access = free }}</ref>

Renaturation of a completely denatured prion to infectious status has not yet been achieved; however, partially denatured prions can be renatured to an infective status under certain artificial conditions.<ref>{{cite journal | vauthors = Weissmann C, Enari M, Klöhn PC, Rossi D, Flechsig E | title = Transmission of prions | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = s 4 | pages = 16378–83 | date = December 2002 | pmid = 12181490 | pmc = 139897 | doi = 10.1073/pnas.172403799 | doi-access = free | bibcode = 2002PNAS...9916378W }}</ref>