litaba

Hangata mosebetsi oa ho etsa ente o hlalosoa e le oa ho hloka teboho. Ho latela mantsoe a Bill Foege, e mong oa lingaka tse kholo ka ho fetisisa lefatšeng tsa bophelo bo botle ba sechaba, “Ha ho motho ea tla le leboha ka ho ba pholosa lefung leo a neng a sa tsebe hore o na le lona.”

Empa lingaka tsa bophelo bo botle ba sechaba li pheha khang ea hore phaello ea matsete e holimo haholo hobane liente li thibela lefu le bokooa, haholo-holo ho bana. Joale ke hobane'ng ha re sa etse liente tsa mafu a mang a thibeloang ke ente? Lebaka ke hore liente li tlameha ho sebetsa hantle le ho bolokeha e le hore li ka sebelisoa ho batho ba phetseng hantle, e leng se etsang hore ts'ebetso ea ntlafatso ea ente e be telele le e thata.

Pele ho 2020, nako e tloaelehileng ho tloha kemolong ea pele ho isa ho laesense ea liente e ne e le lilemo tse 10 ho isa ho tse 15, 'me nako e khuts'oane e le lilemo tse nne (ente ea mumps). Ho theha ente ea COVID-19 ka likhoeli tse 11 ke mosebetsi o makatsang, o entsoeng ke lilemo tsa lipatlisiso tsa mantlha mabapi le sethala se secha sa ente, haholo-holo mRNA. Har'a bona, menehelo ea Drew Weissman le Dr. Katalin Kariko, ba amohetseng Moputso oa 2021 Lasker Clinical Medical Research, ke ba bohlokoa ka ho khetheha.

Molao-motheo oa liente tsa nucleic acid o thehiloe molaong o bohareng oa Watson le Crick oa hore DNA e ngotsoe ho mRNA, mme mRNA e fetoleloa ho liprotheine. Hoo e ka bang lilemo tse 30 tse fetileng, ho ile ha bontšoa hore ho hlahisa DNA kapa mRNA ka seleng kapa ntho leha e le efe e phelang e ka hlahisa liprotheine tse khethiloeng ke tatellano ea nucleic acid. Nakoana ka mor'a moo, mohopolo oa ente ea nucleic acid o ile oa netefatsoa kamora hore liprotheine tse hlahisitsoeng ke DNA ea kantle ho naha li bonts'itsoe ho thusa karabelo ea 'mele ea ho itšireletsa mafung. Leha ho le joalo, ts'ebeliso ea lefats'e ea 'nete ea liente tsa DNA e fokotsehile, qalong ka lebaka la mathata a polokeho a amanang le ho kopanya DNA ho genome ea motho, 'me hamorao ka lebaka la bothata ba ho phahamisa phano e nepahetseng ea DNA khubung.

Ka lehlakoreng le leng, mRNA, leha e ka hlaseloa habonolo ke hydrolysis, e bonahala e le bonolo ho e sebelisa hobane mRNA e sebetsa ka har'a cytoplasm mme ka hona ha e hloke ho fana ka li-nucleic acid ka har'a khubu. Lilemo tse mashome tsa lipatlisiso tsa mantlha tse entsoeng ke Weissman le Kariko, qalong ka laboratoring ea bona mme hamorao kamora ho fana ka tumello ho lik'hamphani tse peli tsa biotechnology (Moderna le BioNTech), li lebisitse ho ente ea mRNA ho phethahala. Senotlelo sa katleho ea bona e ne e le sefe?

Ba ile ba hlōla litšitiso tse ’maloa. mRNA e lemohuoa ke innate immune system pattern pattern recognition receptors (FIG. 1), ho kenyeletsoa litho tsa lelapa la Toll-like receptor (TLR3 le TLR7/8, e utloang RNA e nang le mefuta e 'meli le e nang le mefuta e le' ngoe, ka ho latellana) le retinoic acid e etsa hore gene I protein (RIG-1) tsela, eo hape e leng lefu la plasmic le ho ruruha ha plasma. Receptor ea ho amohela, e hlokomela RNA le ho etsa lintho tse khutšoane "Mofuta oa tsona o kenyang pele ke kena-kenana le sesole sa 'mele). Kahoo, ho kenya mRNA liphoofolong ho ka baka tšabo, ho fana ka maikutlo a hore palo ea mRNA e ka sebelisoang ho batho e ka fokotsoa e le ho qoba litla-morao tse sa amoheleheng.

Ho hlahloba litsela tsa ho fokotsa ho ruruha, Weissman le Kariko ba ile ba ikemisetsa ho utloisisa tsela eo li-receptor tsa ho lemoha li-pathogen li khethollang pakeng tsa RNA e nkiloeng ka pathogen le RNA ea bona. Ba hlokometse hore li-Rna tse ngata tsa intracellular, joalo ka li-ribosomal Rnas tse ruileng, li fetotsoe haholo 'me li hakanngoa hore liphetoho tsena li lumelletse li-Rna tsa bona hore li balehe tlhokomelo ea 'mele ea ho itšireletsa mafung.

Katleho e kholo e bile ha Weissman le Kariko ba bonts'a hore ho fetola mRNA ka pseudouridine sebakeng sa ouridine ho fokolitse ts'ebetso ea 'mele ea ho itšireletsa mafung ha e ntse e boloka bokhoni ba ho kenyelletsa liprotheine. Phetoho ena e eketsa tlhahiso ea protheine, ho fihlela makhetlo a 1,000 a mRNA e sa fetotsoeng, hobane mRNA e fetotsoeng e baleha ho tsejoa ke protheine kinase R (sensor e hlokomelang RNA ebe e phosphorylates le ho kenya tšebetsong ntlha ea qalo ea phetolelo eIF-2α, kahoo e koala phetolelo ea protheine). Pseudouridine modified mRNA ke mokokotlo oa liente tsa mRNA tse nang le laesense tse entsoeng ke Moderna le Pfizer-Biontech.

Katleho ea ho qetela e bile ho fumana mokhoa o motle oa ho paka mRNA ntle le hydrolysis le mokhoa o motle oa ho e isa ho cytoplasm. Mefuta e mengata ea li-mRNA e lekoa ka mefuta e fapaneng ea liente khahlanong le likokoana-hloko tse ling. Ka 2017, bopaki ba kliniki bo tsoang litekong tse joalo bo bonts'itse hore ho kenngoa le ho tsamaisoa ha liente tsa mRNA tse nang le lipid nanoparticles ho matlafalitse ts'ireletso ea 'mele ha ho ntse ho bolokoa boemo bo laolehang ba polokeho.

Liphuputso tse tšehetsang liphoofolong li bontšitse hore lipid nanoparticles e lebisa lisele tse hlahisang antigen ho ntša lymph nodes le ho thusa karabelo ka ho kenya ts'ebetsong mefuta e itseng ea follicular CD4 helper T cell. Lisele tsena tsa T li ka eketsa tlhahiso ea li-antibody, palo ea lisele tsa plasma tse phetseng nako e telele le tekanyo ea karabelo ea lisele tsa B tse holileng. Liente tse peli tseo hajoale li nang le laesense ea COVID-19 mRNA ka bobeli li sebelisa lipid nanoparticle formulations.

Ka lehlohonolo, tsoelo-pele ena ea lipatlisiso tsa mantlha e entsoe pele ho seoa, ho lumella lik'hamphani tsa meriana ho haha ​​​​katleho ea tsona. Liente tsa mRNA li bolokehile, li sebetsa hantle ebile li hlahisoa ka bongata. Ho se ho fanoe ka litekanyetso tse fetang bilione tsa ente ea mRNA, 'me ho eketsa tlhahiso ho litekanyetso tse limilione tse likete tse 2-4 ka 2021 le 2022 ho tla ba bohlokoa ntoeng ea lefats'e khahlanong le COVID-19. Ka bomalimabe, ho na le ho se lekane ho hoholo ha ho fihlella lisebelisoa tsena tse pholosang bophelo, ka liente tsa mRNA tse tsamaisoang haholo linaheng tse nang le chelete e ngata; 'Me ho fihlela tlhahiso ea ente e fihla holimo, ho se lekane ho tla tsoela pele.

Ka ho pharaletseng, mRNA e tšepisa mafube a macha lefapheng la vaccinology, ho re fa monyetla oa ho thibela mafu a mang a tšoaetsanoang, a kang ho ntlafatsa liente tsa sefuba, le ho etsa liente tsa mafu a kang malaria, HIV, le lefuba tse bolaeang palo e kholo ea bakuli 'me li batla li sa sebetse ka mekhoa e tloaelehileng. Mafu a kang mofetše, ao pele a neng a nkoa a le thata ho sebetsana le 'ona ka lebaka la monyetla o fokolang oa ntlafatso ea ente le tlhokahalo ea liente tsa motho ka mong, joale a ka nahanoa bakeng sa nts'etsopele ea liente. mRNA ha e bue ka liente feela. Limilione tse likete tsa litekanyetso tsa mRNA tseo re li kentseng bakuli ho fihlela joale li pakile polokeho ea bona, li bula tsela bakeng sa liphekolo tse ling tsa RNA joalo ka phetisetso ea protheine, tšitiso ea RNA, le CRISPR-Cas (lihlopha tse tloaelehileng tsa ho pheta-pheta ha li-palindromic tse khutšoane le ho hlophisoa ha liphatsa tsa lefutso tsa Cas endonucrenases). Phetohelo ea RNA e ne e sa tsoa qala.

Liphihlello tsa saense tsa Weissman le Kariko li pholositse bophelo ba batho ba limilione, ’me leeto la mosebetsi oa Kariko le ntse le tsoela pele, eseng hobane le ikhetha, empa hobane le le teng lefatšeng ka bophara. E le motho ea tloaelehileng ea tsoang naheng e 'ngoe ea Europe Bochabela, o ile a fallela United States ho ea phehella litoro tsa hae tsa saense, empa a sokola feela le tsamaiso ea US ea ho ba moahi, lilemo tsa lichelete tse sa tsitsang tsa lipatlisiso le ho theoloa. O bile a lumela ho fokotsa moputso ho boloka lab e ntse e sebetsa le ho tsoela pele ka lipatlisiso tsa hae. Leeto la mahlale la Kariko le bile boima, leo basali ba bangata, bajaki le batho ba fokolang ba sebetsang likolong ba le tsebang. Haeba u kile ua ba le lehlohonolo la ho kopana le Dr. Kariko, o kenyelletsa moelelo oa boikokobetso; E ka 'na eaba mathata a nakong e fetileng a etsa hore a lule a tiile.

Mosebetsi o boima le katleho e kholo ea Weissman le Kariko li emela karolo e 'ngoe le e 'ngoe ea ts'ebetso ea saense. Ha ho mehato, ha ho limaele. Mosebetsi oa bona o telele ebile o boima, o hloka boitelo, bohlale le pono. Leha re sa tlameha ho lebala hore batho ba bangata lefats'eng ka bophara ba ntse ba se na monyetla oa ho fumana liente, rona ba lehlohonolo la ho entoa khahlanong le COVID-19 re leboha melemo ea ts'ireletso ea liente. Re thoholetsa bo-ramahlale ba babeli bao mosebetsi oa bona o tsoileng matsoho o entseng hore liente tsa mRNA e be tsa sebele. Ke kopanela le ba bang ba bangata ho bontšeng teboho ea ka e sa feleng ho bona.