UGonyo lwe-COVID-19 mRNA: Imbali yeNzululwazi kunye noTshintsho loMdlalo kuNyango

Iiprotheyini zentsholongwane zilawulwa njenge-antigen ngendlela yesitofu sokugonya kunye ne-immune system ye-immune system yenza izilwa-buhlungu ezichasene ne-antigen enikiweyo ngaloo ndlela zibonelela ngokhuseleko kulo naluphi na usulelo oluzayo. Okubangela umdla kukuba, esi sisihlandlo sokuqala kwimbali yoluntu ukuba i-mRNA ehambelana nayo ngokwayo inikwe ngendlela yesitofu sokugonya esisebenzisa oomatshini beeseli ukubonisa/ukuguqulela i-antigen/protein. Oku kuguqula ngokufanelekileyo iiseli zomzimba zibe yifektri yokuvelisa i-antigen, enikezela ngokusebenzayo ku khusela ngokuvelisa amajoni omzimba. Ezi zitofu zokugonya ze-mRNA zifunyenwe zikhuselekile kwaye zisebenza kulingo lwezonyango lwabantu. Kwaye, ngoku, i-COVID-19 mRNA isitofu sokugonya i-BNT162b2 (Pfizer/BioNTech) sinikezelwa ebantwini ngokomthetho womthetho. Njengogonyo lokuqala oluvunyiweyo lwe-mRNA, esi sisiganeko esibalulekileyo kwisayensi esizise kwixesha elitsha iyeza kunye nokuhanjiswa kweziyobisi. Oku kuya kubonakala ngokukhawuleza ukusetyenziswa kwe mRNA Itekhnoloji yonyango lomhlaza, uluhlu lwezitofu zokugonya zezinye izifo, kwaye ke ngoko kunokwenzeka ukutshintsha indlela yokusebenza yamayeza kunye nokumila ishishini loxubo mayeza lilonke kwixesha elizayo.  

Ukuba iprotheyini iyadingeka ngaphakathi kwiseli yokunyanga imeko yokugula okanye ukuba isebenze njenge-antigen yophuhliso lwe-immunity esebenzayo, loo proteni kufuneka ihanjiswe kwiseli ngokukhuselekileyo kwifom ephilileyo. Lo isengumsebenzi onyukayo. Ngaba iprotein inokubonakaliswa ngokuthe ngqo kwiseli ngokutofa i-nucleic acid (i-DNA okanye i-RNA) ehambelana nayo, ethi emva koko isebenzisa oomatshini beselula ukuze baveze? 

Iqela labaphandi lafumana ingcamango ye-nucleic acid encoded ichiza laza labonisa okokuqala ngo-1990 ukuba inaliti ethe ngqo. mRNA kwisihlunu sempuku kukhokelele ekubonakalisweni kweprotheyini enekhowudi kwiiseli zezihlunu⁽¹⁾. Oku kwavula amathuba onyango olusekwe kwimfuza, kunye nezitofu ezisekelwe kwimfuza. Olu phuhliso lwathathwa njengobuchwephesha obuphazamisayo ekuya kuthi kulinganiswe ngabo ubugcisa besitofu sexesha elizayo ⁽²⁾.

Inkqubo yokucinga ikhawuleze yasuka 'kwigene-based' ukuya 'mRNA-based' ukudluliselwa kolwazi kuba i-mRNA ibonelele ngeenzuzo ezininzi xa kuthelekiswa DNA njengoko i-mRNA ingadibanisi kwi-genome (kungoko akukho kudityaniswa kwe-genomic eyingozi) kwaye ayiphindi. Inezinto kuphela ezifunekayo ngokuthe ngqo ukubonakaliswa kweprotheni. Ukudibanisa phakathi kwe-RNA ene-single stranded kunqabile. Ngaphezu koko, iyahlukana phakathi kweentsuku ezimbalwa ngaphakathi kweeseli. Ezi mpawu zenza i-mRNA ifaneleke ngakumbi njengolwazi olukhuselekileyo nolwexeshana oluthwele imolekyuli ukuze isebenze njenge vector kuphuhliso lwesitofu sokugonya. ⁽³⁾. Ngenkqubela phambili yetekhnoloji enxulumene ngakumbi nokuhlanganiswa kwee-mRNAs ezinobunjineli ezinekhowudi ezifanelekileyo ezinokungeniswa kwiiseli zokubonisa iprotein, umda wandiswa ngakumbi ukusuka zokugonya kumachiza onyango. Ukusetyenziswa kwe-mRNA kwaqala ukufumana ingqwalasela njengeklasi yeziyobisi kunye nesicelo esinokubakho kwimimandla yomhlaza we-immunotherapies, izitofu zokugonya izifo ezosulelayo, i-mRNA-based induction yeeseli ze-pluripotent stem, ukuhanjiswa okuncediswa kwe-mRNA koyilo lweenuclease zobunjineli be-genome njl. ⁽⁴⁾.  

Ukuvela kwe Ugonyo olusekwe kwi-mRNA kunye nonyango luye lwazaliswa ngakumbi ngeziphumo zolingo lwangaphambili. Ezi zitofu zifunyenwe zifuna impendulo enamandla yokuzikhusela kwizifo ezosulelayo kwiimodeli zezilwanyana zentsholongwane yomkhuhlane, i-Zika virus, i-rabies virus kunye nabanye. Iziphumo ezithembisayo zikwabonwa ngokusebenzisa i-mRNA kulingo lwezonyango zomhlaza ⁽⁵⁾. Ukuqonda amandla orhwebo obuchwephesha, imizi-mveliso yenza utyalo-mali olukhulu lwe-R&D kwizitofu zokugonya ezisekwe kwi-mRNA kunye namachiza. Umzekelo, de kube ngo-2018, iModerna Inc. ⁽⁶⁾. Ngaphandle kwemizamo emanyeneyo yokusetyenziswa kwe-mRNA njengendlela yonyango kwizitofu zokugonya izifo ezosulelayo, ukhuselo lomhlaza, unyango lwezifo zemfuzo kunye nonyango lokubuyisela iproteni, ukusetyenziswa kobuchwephesha be-mRNA kuthintelwe ngenxa yokungazinzi kunye nokuthambekela kokuthotywa ziinucleases. Ukuguqulwa kweekhemikhali ze-mRNA kuncede kancinci kodwa ukuhanjiswa kwe-intracellular kusengumqobo nangona i-lipid-based nanoparticles isetyenziselwa ukuhambisa i-mRNA. ⁽⁷⁾. 

Unyanzeliso lokwenyani kwinkqubela phambili yetekhnoloji ye-mRNA kunyango lweza, ngembeko yemeko embi evezwe lihlabathi jikelele. Covid-19 isifo esikho elizweni jikelele. Uphuhliso lwesitofu sokugonya esikhuselekileyo nesisebenzayo ngokuchasene ne-SARS-CoV-2 yaba yeyona nto iphambili kuye wonke umntu. Ulingo olukhulu lwezonyango lwenziwa ukuqinisekisa ukhuseleko kunye nokusebenza kwesitofu sokugonya se-COVID-19 mRNA BNT162b2 (Pfizer/BioNTech). Ulingo lwaqala nge-10 kaJanuwari 2020. Emva kweenyanga ezimalunga neshumi elinanye zomsebenzi onzima, idatha evela kuphononongo lwezonyango yangqina ukuba i-COVID-19 iyathintelwa ngogonyo kusetyenziswa i-BNT162b2. Oku kubonelele ngobungqina bokuba isitofu sokugonya esisekwe kwi-mRNA sinokubonelela ngokhuseleko kusulelo. Umceli mngeni ongazange ubonwe ngaphambili owenziwe ngubhubhane wanceda ubungqina bokuba isitofu sokugonya esekwe kwi-mRNA sinokuphuhliswa ngokukhawuleza, ukuba izixhobo ezaneleyo zenziwe zifumaneke. ⁽⁸⁾. Isitofu sokugonya se-mRNA sikaModerna sikwafumene isigunyaziso sosetyenziso olungxamisekileyo yi-FDA kwinyanga ephelileyo.

Zombini i-COVID-19 Amayeza okugonya e-mRNA okt, BNT162b2 of Pfizer/BioNTech kunye Imoderna I-mRNA-1273 ngoku isetyenziselwa ukugonya abantu ngokwemigaqo yelizwe yolawulo lwesitofu sokugonya. ⁽⁹⁾.

Impumelelo ezimbini Covid-19 Ugonyo lwe-mRNA (BNT162b2 ye-Pfizer/BioNTech kunye ne-Moderna's mRNA-1273) kulingo lwezonyango kunye nolwamkelo lwazo lwalandelayo lokusetyenziswa linyathelo elibalulekileyo kwinzululwazi nakunyango. Oku kubonakalise ubuchwephesha obungangqinwanga ukuza kuthi ga ngoku, obuphezulu obuphezulu obufunwa luluntu lwezenzululwazi kunye neshishini lamayeza malunga namashumi amathathu eminyaka. ⁽¹⁰⁾.   

Umdla omtsha olandela le mpumelelo unyanzelekile ukuba uqokelele amandla emva kobhubhani kwaye unyango lwe-mRNA luya kungqina ukuba bubuchwephesha obuphazamisayo obuzisa ixesha elitsha kwezamayeza kunye nesayensi yokuhanjiswa kweziyobisi.   

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DOI: https://doi.org/10.29198/scieu/2012291  

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