labarai

Ana kwatanta aikin yin maganin alurar riga kafi da rashin godiya. A cikin kalmomin Bill Foege, ɗaya daga cikin manyan likitocin kiwon lafiyar jama'a a duniya, "Babu wanda zai gode maka don ceton su daga wata cuta da ba ta taɓa sanin suna da ita ba."

Amma likitocin kiwon lafiyar jama'a suna jayayya cewa dawowar jarin yana da yawa sosai saboda alluran rigakafi suna hana mutuwa da nakasa, musamman ga yara. Don haka me ya sa ba mu yin alluran rigakafi don ƙarin cututtukan da za a iya rigakafin rigakafi? Dalili kuwa shi ne, dole ne alluran rigakafin su kasance masu inganci da aminci ta yadda za a iya amfani da su a cikin mutane masu lafiya, wanda ke sa tsarin samar da rigakafin ya daɗe da wahala.

Kafin shekarar 2020, matsakaicin lokacin daga tunanin farko zuwa lasisin alluran rigakafin shine shekaru 10 zuwa 15, mafi ƙarancin lokacin shine shekaru huɗu (alurar rigakafin mumps). Haɓaka maganin COVID-19 a cikin watanni 11 don haka babban abin al'ajabi ne, wanda aka yi shi ta hanyar bincike na asali na shekaru akan sabbin hanyoyin rigakafin, mafi mahimmancin mRNA. Daga cikin su, gudunmawar Drew Weissman da Dr. Katalin Kariko, masu karɓar lambar yabo ta 2021 Lasker Clinical Research Award, suna da mahimmanci.

Ka'idar da ke bayan allurar acid nucleic ta samo asali ne a cikin dokar tsakiya ta Watson da Crick da aka rubuta DNA zuwa mRNA, kuma ana fassara mRNA zuwa sunadarai. Kusan shekaru 30 da suka gabata, an nuna cewa shigar da DNA ko mRNA a cikin tantanin halitta ko kowace halitta mai rai zai bayyana sunadaran da aka ƙaddara ta jerin abubuwan nucleic acid. Ba da daɗewa ba bayan haka, an inganta ra'ayin rigakafin acid nucleic bayan an nuna sunadaran da aka bayyana ta hanyar DNA na waje don haifar da amsawar rigakafi. Koyaya, aikace-aikacen ainihin duniya na allurar DNA an iyakance su, da farko saboda matsalolin tsaro da ke da alaƙa da haɗa DNA cikin kwayar halittar ɗan adam, kuma daga baya saboda wahalar haɓaka ingantaccen isar da DNA a cikin tsakiya.

Sabanin haka, mRNA, ko da yake yana da saukin kamuwa da hydrolysis, ya bayyana yana da sauƙin sarrafa shi saboda ayyukan mRNA a cikin cytoplasm kuma saboda haka baya buƙatar isar da acid nucleic a cikin tsakiya. Shekaru goma na asali na bincike na Weissman da Kariko, da farko a cikin nasu dakin gwaje-gwaje kuma daga baya bayan ba da lasisi ga kamfanonin fasahar kere-kere guda biyu (Moderna da BioNTech), sun haifar da rigakafin mRNA ya zama gaskiya. Menene mabuɗin nasararsu?

Sun shawo kan cikas da yawa. mRNA an gane ta hanyar innate rigakafi tsarin ganewa receptors (FIG. 1), ciki har da mambobi na Toll-kamar receptor iyali (TLR3 da TLR7 / 8, wanda ji sau biyu-stranded da guda-stranded RNA, bi da bi) da kuma retinoic acid haifar da gene I protein (RIG-1) hanya, wanda bi da bi ya haifar da kumburi-1 cell cyG alama ce ta hanyar RIG. Gane gajeriyar RNA mai madauri biyu kuma yana kunna nau'in I interferon, ta haka yana kunna tsarin rigakafi na daidaitacce). Don haka, allurar mRNA a cikin dabbobi na iya haifar da firgita, yana nuna cewa adadin mRNA da za a iya amfani da shi a cikin mutane na iya iyakancewa don guje wa illolin da ba za a yarda da su ba.

Don bincika hanyoyin da za a rage kumburi, Weissman da Kariko sun tashi don fahimtar yadda masu karɓar ƙirar ƙira ke bambanta tsakanin RNA da aka samu pathogen da nasu RNA. Sun lura cewa yawancin Rnas na ciki, irin su ribosomal Rnas masu arziki, an yi su sosai kuma an yi hasashen cewa waɗannan gyare-gyaren sun ba da damar Rna nasu don tserewa ganewar rigakafi.

Wani mahimmin nasara ya zo lokacin da Weissman da Kariko suka nuna cewa gyaggyara mRNA tare da pseudouridine maimakon ouridine yana rage kunnawar rigakafi yayin da yake riƙe da ikon ɓoye sunadaran. Wannan gyare-gyare yana ƙara samar da furotin, har zuwa sau 1,000 na mRNA da ba a canza shi ba, saboda mRNA da aka gyara yana tserewa ganewa ta hanyar gina jiki kinase R (na'urar firikwensin da ke gane RNA sannan kuma phosphorylates kuma yana kunna ma'anar ƙaddamar da fassarar eIF-2a, don haka yana rufe fassarar furotin). Pseudouridine modified mRNA shine kashin bayan lasisin rigakafin mRNA wanda Moderna da Pfizer-Biontech suka haɓaka.

Nasarar ƙarshe ita ce tantance hanya mafi kyau don haɗa mRNA ba tare da hydrolysis ba kuma hanya mafi kyau don isar da shi cikin cytoplasm. An gwada nau'ikan mRNA da yawa a cikin nau'ikan alluran rigakafi daga wasu ƙwayoyin cuta. A cikin 2017, shaidun asibiti daga irin waɗannan gwaje-gwajen sun nuna cewa ƙaddamarwa da isar da allurar rigakafin mRNA tare da ƙwayoyin nanoparticles na lipid sun haɓaka rigakafi yayin da suke kiyaye bayanin martabar aminci.

Taimakon karatu a cikin dabbobi ya nuna cewa lipid nanoparticles sun yi niyya ga sel masu gabatar da antigen a cikin zubar da nodes na lymph kuma suna taimakawa amsa ta hanyar kunna takamaiman nau'ikan CD4 masu taimako na T. Waɗannan ƙwayoyin T suna iya haɓaka samar da rigakafin ƙwayoyin cuta, adadin ƙwayoyin plasma na dogon lokaci da kuma matakin balagaggen amsawar cell B. Su biyun a halin yanzu masu lasisi na COVID-19 mRNA duk suna amfani da tsarin nanoparticle na lipid.

Abin farin ciki, waɗannan ci gaban bincike na asali an yi su ne kafin barkewar cutar, wanda ya baiwa kamfanonin harhada magunguna damar haɓaka nasararsu. allurar rigakafin mRNA amintattu ne, masu inganci kuma ana samarwa da yawa. Fiye da allurai biliyan 1 na rigakafin mRNA an gudanar da su, kuma haɓaka samarwa zuwa allurai biliyan 2-4 a cikin 2021 da 2022 zai zama mahimmanci ga yaƙin duniya na COVID-19. Abin baƙin ciki shine, akwai gagarumin rashin daidaito wajen samun waɗannan kayan aikin ceton rai, tare da allurar rigakafin mRNA a halin yanzu ana gudanar da su galibi a cikin ƙasashe masu tasowa; Kuma har sai samar da allurar rigakafin ya kai iyakarsa, rashin daidaito zai dawwama.

Fiye da haka, mRNA ya yi alkawarin sabon alfijir a fagen ilimin rigakafi, yana ba mu damar rigakafin sauran cututtuka, kamar inganta rigakafin mura, da samar da alluran rigakafin cututtuka irin su zazzabin cizon sauro, HIV, da tarin fuka da ke kashe adadi mai yawa na marasa lafiya kuma ba su da tasiri ta hanyar al'ada. Cututtuka irin su kansar, waɗanda a baya an yi la’akari da su da wahala a magance su saboda ƙarancin yuwuwar ci gaban rigakafin da kuma buƙatar rigakafin keɓaɓɓu, yanzu ana iya la’akari da su don haɓakar rigakafin. mRNA ba game da alluran rigakafi ba ne kawai. biliyoyin allurai na mRNA da muka yi wa marasa lafiya har zuwa yau sun tabbatar da amincin su, suna ba da hanya ga sauran hanyoyin kwantar da hankali na RNA kamar su maye gurbin furotin, tsangwama RNA, da CRISPR-Cas (gungu na yau da kullun na gajerun gajerun maimaitawa na palindromic da ke hade da Cas endonucrenases) gyaran kwayoyin halitta. Juyin juya halin RNA ya fara.

Nasarar kimiyyar Weissman da Kariko sun ceci miliyoyin rayuka, kuma tafiyar aikin Kariko tana tafiya ne, ba wai don ta bambanta ba, amma don duniya ce. Ba kowa daga wata ƙasa ta Gabashin Turai, ta yi ƙaura zuwa Amurka don cim ma burinta na kimiyya, sai dai ta yi fama da tsarin mulkin Amurka, na tsawon shekaru na tallafin bincike mai tsauri, da raguwa. Har ma ta amince za ta rage albashi don ci gaba da gudanar da binciken ta. Tafiyar ilimin kimiyyar Kariko ta kasance mai wuyar gaske, wadda mata da dama da baƙi da ƴan tsiraru da ke aiki a makarantun ilimi suka sani. Idan kun taba samun sa'ar haduwa da Dr. Kariko, ta kunshi ma'anar tawali'u; Watakila wahalhalun da ta yi a baya ne ya sa ta yi kasa a gwiwa.

Aiki mai wuyar gaske da manyan nasarorin Weissman da Kariko suna wakiltar kowane bangare na tsarin kimiyya. Babu matakai, babu mil. Aikin su yana da tsayi da wuya, yana buƙatar juriya, hikima da hangen nesa. Duk da yake ba za mu manta da cewa mutane da yawa a duniya har yanzu ba su da damar yin amfani da alluran rigakafi, mu waɗanda suka yi sa'a don a yi musu rigakafin COVID-19 muna godiya ga fa'idodin kariya na rigakafin. Taya murna ga masana kimiyya guda biyu waɗanda fitattun ayyukansu suka sa allurar mRNA ta zama gaskiya. Ina hada kai da wasu da dama wajen mika godiyata a garesu.