COVID-19 tshuaj tiv thaiv mRNA: Ib qho tseem ceeb hauv kev tshawb fawb thiab kev hloov pauv hauv tshuaj

Viral proteins yog muab raws li antigen nyob rau hauv daim ntawv ntawm cov tshuaj tiv thaiv thiab lub cev tiv thaiv kab mob ntawm lub cev tsim cov tshuaj tiv thaiv rau cov antigen muab yog li muab kev tiv thaiv tiv thaiv tej yam kab mob yav tom ntej. Interestingly, qhov no yog thawj zaug nyob rau hauv tib neeg keeb kwm uas coj mRNA nws tus kheej yog muab nyob rau hauv daim ntawv ntawm ib tug tshuaj tiv thaiv uas siv lub cell machinery rau kev qhia / txhais ntawm antigen / protein. Qhov no zoo hloov cov hlwb ntawm lub cev mus rau hauv lub Hoobkas tsim cov antigen, uas nyob rau hauv lem muab active kev tiv thaiv los ntawm kev tsim cov tshuaj tiv thaiv. Cov tshuaj tiv thaiv mRNA no tau pom tias muaj kev nyab xeeb thiab siv tau zoo hauv tib neeg kev sim tshuaj. Thiab tam sim no, COVID-19 mRNA tshuaj tiv thaiv BNT162b2 (Pfizer/BioNTech) tau muab rau cov neeg raws li txoj cai. Raws li thawj zaug pom zoo tshuaj tiv thaiv mRNA, qhov no yog qhov tseem ceeb hauv kev tshawb fawb uas tau coj mus rau lub sijhawm tshiab hauv tshuaj thiab xa tshuaj. Qhov no tuaj yeem pom sai sai ntawm daim ntawv thov mRNA thev naus laus zis rau kev kho mob qog noj ntshav, ntau yam tshuaj tiv thaiv rau lwm yam kab mob, thiab yog li muaj peev xwm hloov pauv kev coj noj coj ua thiab kev lag luam kws tshuaj zoo rau yav tom ntej.  

Yog tias xav tau cov protein nyob hauv lub cell los kho cov kab mob los yog ua raws li cov tshuaj tiv thaiv kab mob rau kev loj hlob ntawm kev tiv thaiv kab mob, cov protein yuav tsum tau xa mus rau hauv lub cell kom nyab xeeb hauv daim ntawv tsis zoo. Qhov no tseem yog txoj haujlwm nce toj. Cov protein puas tuaj yeem qhia ncaj qha rau hauv lub cell los ntawm kev txhaj tshuaj nucleic acid (DNA lossis RNA), uas tom qab ntawd siv cov tshuab ntawm tes rau kev qhia? 

Ib pawg ntawm cov kws tshawb fawb tau tsim lub tswv yim ntawm nucleic acid encoded tshuaj thiab tau pom thawj zaug hauv xyoo 1990 tias kev txhaj tshuaj ncaj qha. mRNA nyob rau hauv cov nqaij nas coj mus rau kev qhia ntawm encoded protein nyob rau hauv cov nqaij hlwb⁽¹⁾. Qhov no tau qhib qhov muaj peev xwm ntawm kev kho cov noob caj noob ces, nrog rau cov tshuaj tiv thaiv kab mob. Qhov kev txhim kho no tau raug suav tias yog kev cuam tshuam kev siv thev naus laus zis tiv thaiv cov cuab yeej tshuaj tiv thaiv yav tom ntej yuav raug ntsuas ⁽²⁾.

Cov txheej txheem kev xav sai sai ntawm 'gene-based' mus rau 'mRNA-based 'cov ntaub ntawv hloov pauv vim mRNA muaj ntau qhov zoo piv rau DNA raws li mRNA tsis sib koom ua ke hauv genome (li no tsis muaj kev cuam tshuam genomic kev koom ua ke) lossis nws tsis rov ua dua. Nws tsuas muaj cov ntsiab lus ncaj qha rau kev qhia cov protein. Recombination ntawm ib leeg stranded RNA yog tsawg. Ntxiv mus, nws disintegrates nyob rau hauv ob peb hnub nyob rau hauv lub hlwb. Cov yam ntxwv no ua rau mRNA tsim nyog raws li cov ntaub ntawv muaj kev nyab xeeb thiab ntu ntu nqa cov khoom siv los ua tus vector rau kev tsim tshuaj tiv thaiv kab mob. ⁽³⁾. Nrog rau kev nce qib hauv thev naus laus zis tshwj xeeb tshaj yog hais txog kev sib txuas ntawm kev tsim kho mRNAs nrog cov lej zoo uas tuaj yeem xa mus rau hauv cov hlwb rau cov lus qhia protein, qhov kev nthuav dav ntxiv los ntawm tshuaj tiv thaiv rau cov tshuaj kho mob. Kev siv mRNA pib tau txais kev saib xyuas raws li chav kawm tshuaj uas muaj peev xwm siv tau hauv thaj chaw ntawm kev tiv thaiv kab mob qog noj ntshav, tshuaj tiv thaiv kab mob sib kis, mRNA-raws li induction ntawm pluripotent qia hlwb, mRNA-pab xa cov qauv tsim nucleases rau genome engineering thiab lwm yam. ⁽⁴⁾.  

Kev tshwm sim ntawm tshuaj tiv thaiv mRNA thiab cov kws kho mob tau txais txiaj ntsig ntxiv los ntawm cov txiaj ntsig los ntawm kev sim ua ntej. Cov tshuaj tiv thaiv no tau pom los txhawb lub zog tiv thaiv kab mob tiv thaiv kab mob sib kis hauv cov tsiaj qauv ntawm tus kab mob khaub thuas, tus kab mob Zika, kab mob rabies thiab lwm yam. Cov txiaj ntsig tau lees paub kuj tau pom los ntawm kev siv mRNA hauv kev sim tshuaj kho mob qog noj ntshav ⁽⁵⁾. Kev paub txog kev lag luam muaj peev xwm ntawm thev naus laus zis, kev lag luam tau nqis peev R & D loj hauv mRNA-based tshuaj tiv thaiv thiab tshuaj. Piv txwv li, kom txog rau thaum 2018, Moderna Inc. tej zaum yuav tau nqis peev ntau tshaj li ib txhiab daus las thaum tseem xyoo nyob deb ntawm txhua yam khoom lag luam. ⁽⁶⁾. Txawm hais tias muaj kev sib koom ua ke ntawm kev siv mRNA raws li kev kho mob hauv cov tshuaj tiv thaiv kab mob sib kis, kev tiv thaiv kab mob qog noj ntshav, kev kho cov kab mob caj ces thiab kev kho cov protein hloov pauv, kev siv mRNA thev naus laus zis tau txwv vim nws tsis ruaj khov thiab muaj kev cuam tshuam rau kev puas tsuaj los ntawm nucleases. Kev hloov kho tshuaj ntawm mRNA tau pab me ntsis tab sis kev xa tawm hauv lub cev tseem tseem muaj teeb meem txawm hais tias lipid-based nanoparticles tau siv los xa mRNA. ⁽⁷⁾. 

Kev txhawb siab tiag tiag rau kev nce qib ntawm mRNA thev naus laus zis rau kev kho mob tuaj, kev saib xyuas tsis zoo uas tshwm sim los ntawm thoob ntiaj teb Covid-19 kev kis kab mob mus thoob. Kev tsim cov tshuaj tiv thaiv zoo thiab muaj txiaj ntsig tiv thaiv SARS-CoV-2 tau dhau los ua qhov tseem ceeb tshaj plaws rau txhua tus. Kev sim ntau qhov chaw kho mob loj loj tau ua los txhawm rau paub tseeb tias muaj kev nyab xeeb thiab ua haujlwm tau zoo ntawm COVID-19 mRNA tshuaj tiv thaiv BNT162b2 (Pfizer/BioNTech). Kev sim pib thaum Lub Ib Hlis 10, 2020. Tom qab li kaum ib lub hlis ntawm kev ua haujlwm nruj, cov ntaub ntawv los ntawm kev tshawb fawb soj ntsuam tau ua pov thawj tias COVID-19 tiv thaiv tau los ntawm kev txhaj tshuaj tiv thaiv siv BNT162b2. Qhov no tau muab pov thawj ntawm lub tswv yim tias cov tshuaj tiv thaiv mRNA tuaj yeem muab kev tiv thaiv kab mob. Qhov kev sib tw uas tsis tau muaj dua los ntawm kev sib kis tau pab ua pov thawj tias cov tshuaj tiv thaiv mRNA tuaj yeem tsim tau nrawm, yog tias muaj peev txheej txaus ⁽⁸⁾. Moderna cov tshuaj tiv thaiv mRNA kuj tau txais kev tso cai siv thaum muaj xwm ceev los ntawm FDA lub hli tas los.

Ob qhov COVID-19 mRNA tshuaj tiv thaiv ie, BNT162b2 ntawm Pfizer/BioNTech thiab Niaj hnub nimno mRNA-1273 tam sim no tau siv los txhaj tshuaj tiv thaiv tib neeg raws li kev cai hauv tebchaws rau kev tswj hwm tshuaj tiv thaiv ⁽⁹⁾.

Kev vam meej ntawm ob Covid-19 mRNA (BNT162b2 ntawm Pfizer/BioNTech thiab Moderna's mRNA-1273) cov tshuaj tiv thaiv hauv kev sim tshuaj thiab lawv qhov kev pom zoo tom qab siv yog qhov tseem ceeb hauv kev tshawb fawb thiab tshuaj. Qhov no tau ua pov thawj txog tam sim no tsis muaj pov thawj, muaj peev xwm kho mob tau zoo uas lub zej zog kev tshawb fawb thiab kev lag luam tshuaj tau nrhiav tau yuav luag peb xyoo lawm. ⁽¹⁰⁾.   

Qhov kev txaus siab tshiab tom qab qhov kev vam meej no yog ua kom sib sau ua ke lub zog tom qab muaj kev sib kis thiab mRNA cov kws kho mob yuav ua pov thawj ntxiv los ua kev cuam tshuam kev siv thev naus laus zis hauv lub sijhawm tshiab hauv tshuaj thiab kev tshawb fawb ntawm kev xa tshuaj.   

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

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