amakuru

Akazi ko gukora urukingo gakunze gusobanurwa nkudashima. Mu magambo ya Bill Foege, umwe mu baganga bakomeye ku buzima rusange ku isi, yagize ati: “Ntawe uzagushimira ko wabakijije indwara batigeze bamenya ko bafite.”

Ariko abaganga b’ubuzima rusange bavuga ko inyungu ku ishoramari ari nyinshi cyane kuko inkingo zibuza urupfu n’ubumuga, cyane cyane ku bana. None se kuki tutakora inkingo zindwara nyinshi zishobora kwirindwa? Impamvu nuko inkingo zigomba kuba nziza kandi zifite umutekano kugirango zishobore gukoreshwa mubantu bazima, ibyo bigatuma inzira yiterambere ryinkingo iba ndende kandi igoye.

Mbere ya 2020, impuzandengo kuva igihe cyo gusama kugeza gutanga uruhushya rwinkingo yari imyaka 10 kugeza kuri 15, mugihe gito ni imyaka ine (urukingo rwa mumps). Gutezimbere urukingo rwa COVID-19 mumezi 11 rero nibikorwa bidasanzwe, byashobokaga mumyaka yubushakashatsi bwibanze ku mbuga nshya z’inkingo, cyane cyane mRNA. Muri bo, uruhare rwa Drew Weissman na Dr. Katalin Kariko, abahawe igihembo cya 2021 cya Lasker Clinical Medical Research Award, ni ingenzi cyane.

Ihame riri inyuma yinkingo za aside nucleique yashinze imizi mu itegeko rikuru rya Watson na Crick rivuga ko ADN yanditswe muri mRNA, naho mRNA igahinduka poroteyine. Hafi yimyaka 30 ishize, herekanywe ko kwinjiza ADN cyangwa mRNA mu ngirabuzimafatizo cyangwa ibinyabuzima byose byerekana poroteyine zagenwe na aside nucleique ikurikirana. Nyuma yaho gato, igitekerezo cyo gukingira aside nucleic cyemejwe nyuma yuko poroteyine zagaragajwe na ADN zidasanzwe zerekanwe ko zitanga ubudahangarwa bw'umubiri. Ariko, kwisi-nyayo ikoreshwa ryinkingo za ADN zaragabanutse, ubanza kubera impungenge z'umutekano zijyanye no kwinjiza ADN muri genomuntu, hanyuma kubera ikibazo cyo kwaguka neza kwa ADN muri nucleus.

Ibinyuranye, mRNA, nubwo ishobora kwanduzwa na hydrolysis, isa nkaho yoroshye kuyikoresha kuko mRNA ikora muri cytoplazme bityo ntikeneye gutanga aside nucleique muri nucleus. Imyaka myinshi yubushakashatsi bwibanze bwakozwe na Weissman na Kariko, ubanza muri laboratoire yabo nyuma nyuma yo gutanga uruhushya mubigo bibiri byikoranabuhanga (Moderna na BioNTech), byatumye urukingo rwa mRNA ruba impamo. Ni uruhe rufunguzo rwo gutsinda kwabo?

Batsinze inzitizi nyinshi. mRNA izwi na sisitemu yubudahangarwa bw'umubiri (FIG. 1), harimo n'abagize umuryango wa Toll umeze nka Toll (TLR3 na TLR7 / 8, wumva RNA ikubye kabiri kandi ifite umurongo umwe), kandi aside retinoic itera inzira ya poroteyine ya I I (RIG-1), nayo ikabyara inzira ya RNA, bityo ukore sisitemu yo kurwanya imihindagurikire y'ikirere). Gutyo, gutera mRNA mu nyamaswa birashobora gutera ihungabana, byerekana ko ingano ya mRNA ishobora gukoreshwa mubantu ishobora kuba mike kugirango birinde ingaruka zitemewe.

Kugira ngo hamenyekane uburyo bwo kugabanya umuriro, Weissman na Kariko bahisemo gusobanukirwa uburyo ibyakirwa byerekana imiterere itandukanya RNA ikomoka kuri virusi na RNA yabo. Babonye ko Rnas nyinshi zidasanzwe, nka Rnas ikungahaye kuri ribosomal, zahinduwe cyane kandi bavuga ko ibyo byahinduye byatumye Rnasi zabo zitamenyekana.

Iterambere ryingenzi ryabaye igihe Weissman na Kariko berekanaga ko guhindura mRNA hamwe na pseudouridine aho kuba usidine byagabanije gukora ubudahangarwa bw'umubiri mu gihe bigumana ubushobozi bwo kubika poroteyine. Ihinduka ryongera umusaruro wa poroteyine, inshuro zigera ku 1.000 za mRNA idahinduwe, kubera ko mRNA yahinduwe ihunga kumenyekana na protein kinase R (sensor imenya RNA hanyuma fosifori kandi igakora ibintu byo gutangiza ibisobanuro eIF-2α, bityo igahagarika ibisobanuro bya poroteyine). Pseudouridine yahinduwe mRNA ninkingi yinkingo za mRNA zemewe zakozwe na Moderna na Pfizer-Biontech.

Iterambere ryanyuma kwari ukumenya inzira nziza yo gupakira mRNA idafite hydrolysis nuburyo bwiza bwo kuyigeza muri cytoplazme. Imiti myinshi ya mRNA yapimwe mu nkingo zitandukanye zirwanya izindi virusi. Muri 2017, ibimenyetso by’amavuriro bivuye muri ibyo bigeragezo byagaragaje ko gukusanya no gutanga inkingo za mRNA hamwe na lipide nanoparticles byongereye ubudahangarwa bw'umubiri mu gihe bikomeza umutekano ucungwa.

Gushyigikira ubushakashatsi ku nyamaswa byagaragaje ko lipide nanoparticles yibasira ingirabuzimafatizo zerekana antigen mu kuvoma lymph node kandi igafasha igisubizo itera gukora ubwoko bwihariye bwimikorere ya CD4 ifasha T. Utugingo ngengabuzima T dushobora kongera umusaruro wa antibody, umubare wama selile ya plasma uramba hamwe nurwego rwa B ikuze. Inkingo zombi zifite uruhushya rwa COVID-19 mRNA zombi zikoresha lipide nanoparticle.

Ku bw'amahirwe, iri terambere mu bushakashatsi bwibanze ryakozwe mbere y’icyorezo, bituma ibigo bikorerwamo ibya farumasi byubaka ku ntsinzi yabyo. inkingo za mRNA zifite umutekano, zifite akamaro kandi zakozwe cyane. Hatanzwe dosiye zirenga miliyari 1 z'urukingo rwa mRNA, kandi kugeza umusaruro kugeza kuri miliyari 2-4 muri 2021 na 2022 bizaba ingenzi mu kurwanya isi yose kurwanya COVID-19. Kubwamahirwe, hari ubusumbane bugaragara muburyo bwo kubona ibyo bikoresho bikiza ubuzima, hamwe ninkingo za mRNA zitangwa cyane cyane mubihugu byinjiza amafaranga menshi; Kandi kugeza igihe inkingo zigeze ku ntera ntarengwa, ubusumbane buzakomeza.

Muri rusange, mRNA isezeranya umuseke mushya mu bijyanye n’inkingo, iduha amahirwe yo gukumira izindi ndwara zanduza, nko kunoza inkingo z’ibicurane, no guteza imbere inkingo z’indwara nka malariya, virusi itera sida, n’igituntu zica umubare munini w’abarwayi kandi usanga zidakora neza n’uburyo busanzwe. Indwara nka kanseri, zafatwaga nk'izigoye guhangana nazo kubera ko bishoboka ko iterambere ry’inkingo nkeya ndetse no gukenera inkingo zihariye, ubu zishobora gutekerezwa hagamijwe iterambere ry’inkingo. mRNA ntabwo ireba inkingo gusa. Amamiliyaridi ya dosiye ya mRNA twinjije mu barwayi kugeza ubu yerekanye umutekano wabo, itanga inzira ku bundi buryo bwo kuvura RNA nko gusimbuza poroteyine, kwivanga kwa RNA, hamwe na CRISPR-Cas (ihuriro risanzwe rya interineti ihuriweho na palindromic bigaruka hamwe na Cas endonucrenase). Impinduramatwara ya RNA yari itangiye.

Ubumenyi bwa Weissman na Kariko bwarokoye abantu babarirwa muri za miriyoni, kandi urugendo rwa Kariko rugenda, ntabwo ari ukubera ko rwihariye, ahubwo ni rusange. Umuntu usanzwe ukomoka mu bihugu by’Uburayi bw’iburasirazuba, yimukiye muri Amerika kugira ngo akurikirane inzozi ze za siyansi, gusa arwana na gahunda yo kuyobora Amerika, imyaka myinshi yatewe inkunga n’ubushakashatsi, ndetse no kumanuka. Ndetse yemeye kugabanya umushahara kugirango laboratoire ikomeze kandi akomeze ubushakashatsi bwe. Urugendo rwa siyansi rwa Kariko rwabaye ingorabahizi, urugendo abagore benshi, abimukira n’abato bakora muri za kaminuza. Niba warigeze kugira amahirwe yo guhura na Dr. Kariko, akubiyemo ibisobanuro byo kwicisha bugufi; Birashoboka ko ingorane zashize zamuteye gukomeza.

Imirimo ikomeye nibikorwa bikomeye bya Weissman na Kariko byerekana ibintu byose byubumenyi. Nta ntambwe, nta kilometero. Igikorwa cabo ni kirekire kandi kirakomeye, gisaba gushikama, ubwenge no kwerekwa. Nubwo tutagomba kwibagirwa ko abantu benshi kwisi batarabona inkingo, abo muri twe bagize amahirwe yo gukingirwa COVID-19 twishimiye inyungu zo gukingira inkingo. Ndashimira abahanga babiri shingiro umurimo wabo wingenzi watumye inkingo za mRNA ziba impamo. Nifatanije nabandi benshi mubashimira byimazeyo.