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Na Mgbakọ Vaccine na Health Conference, ndị ọkachamara kpọrọ oku maka "onye ọ bụla kwesịrị ịṅa ntị na ọgwụ mgbochi mRNA, nke na-enye mmadụ echiche na-akparaghị ókè."Yabụ kedu ihe bụ ọgwụ mgbochi mRNA?Kedu ka esi achọpụta ya na gịnị bụ uru ngwa ya?Ọ nwere ike iguzogide iwe COVID-19 gburugburu ụwa?Obodo m enweela ọgwụ mgbochi mRNA nke ọma?Taa, ka anyị mụta maka oge gara aga na ugbu a nke ọgwụ mgbochi mRNA.

01
Kedu ihe bụ mRNA na ọgwụ mgbochi mRNA?

mRNA (Onye ozi RNA), ya bụ, onye ozi RNA, bụ ụdị RNA nwere otu eriri nke edere site na eriri DNA dị ka ndebiri ma na-ebu ozi mkpụrụ ndụ ihe nketa nwere ike iduzi njikọ protein.N'okwu ndị nkịtị, mRNA na-emegharị ozi mkpụrụ ndụ ihe nketa nke otu eriri DNA nwere eriri abụọ n'ime oghere, wee hapụ oghere ahụ iji mepụta protein na cytoplasm.Na cytoplasm, ribosomes na-aga n'akụkụ mRNA, gụọ usoro ntọala ya, wee tụgharịa ya n'ime amino acid kwekọrọ na ya, n'ikpeazụ na-etolite protein (Fig 1).

1

Ọgụgụ 1 mRNA usoro ọrụ

02
Kedu ihe bụ ọgwụ mgbochi mRNA na gịnị na-eme ka ọ bụrụ ihe pụrụ iche?

MRNA ịgba ọgwụ mgbochi ọrịa na-ewebata mRNA na-edobe antigens ọrịa kpọmkwem n'ime ahụ, ma na-eji usoro protein protein cell cell na-emepụta antigens, si otú ahụ na-ebute nzaghachi mgbochi.Ọtụtụ mgbe, enwere ike ịrụ usoro mRNA nke antigens kpọmkwem dị ka ọrịa dị iche iche si dị, chịkọta ma bufee ya n'ime mkpụrụ ndụ site na mkpụrụ ndụ lipid nanocarrier, wee jiri usoro mRNA nke ribosomes mmadụ mee ihe iji sụgharịa usoro mRNA iji mepụta protein antigen ọrịa, bụ nke sistemu autoimmune na-amata mgbe ihe nzuzo gachara dị ka ọrịa na-alụso ọrịa ọgụ.

3Onyonyo 2. In vivo mmetụta nke ogwu mRNA

Yabụ, kedu ihe pụrụ iche gbasara ụdị ọgwụ mgbochi mRNA a ma e jiri ya tụnyere ọgwụ mgbochi ọdịnala?Ọgwụ mgbochi mRNA bụ ọgwụ mgbochi ọgbọ nke atọ kacha egbu egbu, a ga-achọkwa nyocha ọzọ iji welie nkwụsi ike ha, mezie immunogenicity ha, na ịzụlite teknụzụ nnyefe ọhụrụ.

Ọgbọ mbụ nke ọgwụ mgbochi ọdịnala na-agụnyekarị ọgwụ mgbochi arụghị ọrụ na ọgwụ mgbochi ndụ, bụ nke a na-ejikarị eme ihe.Ọgwụ mgbochi ọrịa na-ezo aka na mbụ ịzụlite nje ma ọ bụ nje bacteria, wee jiri okpomọkụ ma ọ bụ kemịkal mee ka ha rụọ ọrụ (na-abụkarị formalin);Ọgwụ mgbochi ndụ ndụ na-ezo aka na nje nje na-agbanwe ma na-ebelata nsi ha mgbe ọgwụgwọ dị iche iche gasịrị.mana ka na-ejigide immunogenicity ya.Ịbanye ya n'ime ahụ agaghị eme ka ọrịa pụta, ma nje na-akpata ọrịa nwere ike itolite ma mụbaa n'ime ahụ, kpalite mmeghachi omume mgbochi nke ahụ, ma na-ekere òkè n'inweta nchebe ogologo oge ma ọ bụ ogologo ndụ.

Ọgbọ nke abụọ nke ọgwụ mgbochi ọhụrụ gụnyere ọgwụ mgbochi subunit na ọgwụ mgbochi protein recombinant.Mgbochi Subunit bụ ọgwụ mgbochi mgbochi nke isi ihe mgbochi immunogen nke nje bacteria na-echebe, ya bụ, site na ire kemịkalụ ma ọ bụ proteolysis a na-achịkwa, a na-ewepụta ma na-enyocha usoro protein pụrụ iche nke nje bacteria na nje.Vaccines mere nke immunologically arụ ọrụ iberibe;ọgwụ mgbochi protein recombinant bụ protein recombinant antigen emepụtara n'ime usoro okwu cell dị iche iche.

Ọgbọ nke atọ nke ọgwụ mgbochi oke gụnyere ọgwụ mgbochi DNA na ọgwụ mgbochi mRNA.Ọ bụ iwebata mkpụrụ ndụ nje viral ozugbo (DNA ma ọ bụ RNA) na-edobe ụfọdụ protein antigenic n'ime sel somatic anụmanụ (ịgba ọgwụ mgbochi n'ime ahụ mmadụ), wee mepụta protein antigenic site na sistemu protein protein nke cell nnabata, na-eme ka onye ọbịa mepụta ihe mgbochi na nzaghachi protein antigenic iji nweta ebumnuche mgbochi na ọgwụgwọ ọrịa.Ihe dị iche n'etiti ha abụọ bụ na a na-ebu ụzọ degharịa DNA na mRNA wee mepụta protein, ebe mRNA na-arụ ọrụ ozugbo.

03
Akụkọ nchoputa na uru ngwa nke ogwu mRNA

A bịa n'ihe gbasara ọgwụ mgbochi mRNA, anyị ga-ekwupụtarịrị otu ọkà mmụta sayensị nwanyị pụtara ìhè, Kati Kariko, onye tọrọ ntọala nyocha sayensị siri ike maka ọbịbịa nke ọgwụ mgbochi mRNA.O juputara na mmasị nyocha na mRNA mgbe ọ na-agụ akwụkwọ.N'ime ihe karịrị afọ 40 nke ọrụ nyocha sayensị, ọ nwere ihe ndọghachi azụ ugboro ugboro, o tinyeghị akwụkwọ maka ego nyocha sayensị, na enweghị ọnọdụ nyocha sayensị kwụsiri ike, mana ọ na-esi ọnwụ mgbe niile na nyocha mRNA.

4Kati Karito

Enwere ọnụ atọ dị mkpa na ọbịbịa nke ọgwụ mgbochi mRNA.

Na nzọụkwụ nke mbụ, o nwere ihe ịga nke ọma n'imepụta molekul mRNA a chọrọ site na omenala cell, ma ọ zutere nsogbu n'ime ka mRNA na-arụ ọrụ n'ime ahụ: mgbe ọ gbasasịrị mRNA n'ime òké, usoro ahụ ji alụso ọrịa ọgụ ga-eloda ya.Mgbe ahụ ọ zutere Weissman.Ha jiri molekul dị na tRNA a na-akpọ pseudouridine mee ka mRNA gbanahụ nzaghachi mgbochi ahụ.[2].
Na nzọụkwụ nke abụọ, gburugburu 2000, Prọfesọ Pieter Cullis gụrụ lipid nanotechnology LNPs maka in vivo nnyefe nke siRNA maka gene silencing ngwa [3] [4].Weissman nzukọ Kariko et al.chọpụtara na LNP bụ onye na-ebu mRNA kwesịrị ekwesị na vivo, ma nwee ike bụrụ ngwá ọrụ bara uru maka ịnapụta mRNA na-edobe protein ọgwụgwọ, ma mesịa chọpụta na mgbochi nke nje Zika, HIV na etuto ahụ [5] [6] [7] [8].

Na nzọụkwụ nke atọ, na 2010 na 2013, Moderna na BioNTech nwetara ikikere patent nke metụtara njikọ mRNA sitere na Mahadum Pennsylvania maka mmepe ọzọ.Katalin ghọkwara onye isi osote onye isi oche nke BioNTech na 2013 iji nwetakwuo ọgwụ mgbochi mRNA.

Taa, enwere ike iji ọgwụ mgbochi mRNA mee ihe na ọrịa na-efe efe, etuto ahụ, na ụkwara ume ọkụ.N'ihe gbasara COVID-19 na-ewe iwe gburugburu ụwa, ọgwụ mgbochi mRNA nwere ike rụọ ọrụ dị ka onye nche.

04
Atụmanya ngwa nke ọgwụ mgbochi mRNA na COVID-19

Site na ntiwapụ nke COVID-19 zuru ụwa ọnụ, mba dị iche iche na-agbasi mbọ ike ịmepụta ọgwụ mgbochi iji kwụsị ọrịa ahụ.Dị ka ụdị ọgwụ mgbochi ọhụrụ, ọgwụ mgbochi mRNA ekerewo òkè na-eduga n'ọbịbịa nke ọrịa okpueze ọhụrụ.Ọtụtụ akwụkwọ akụkọ kachasị elu akọpụtala ọrụ mRNA na SARS-CoV-2 coronavirus ọhụrụ (Nyocha 3).

5

Ọnụọgụ 3 Akụkọ banyere ọgwụ mgbochi mRNA iji gbochie coronavirus ọhụrụ (site na NCBI)

Nke mbụ, ọtụtụ ndị ọkà mmụta sayensị akọpụtala nyocha nke ọgwụ mgbochi mRNA (SARS-CoV-2 mRNA) megide coronavirus ọhụrụ na ụmụ oke.Dịka ọmụmaatụ: ọgwụ mgbochi mRNA (mRNA-LNP) lipid nanoparticle-encapsulated-nucleoside-modified mRNA (mRNA-LNP).Nke a na-egosi na ọgwụ mRNA-LNP bụ onye na-ekwe nkwa megide COVID-19[9][10].

Nke abụọ, ụfọdụ ndị ọkà mmụta sayensị tụlere nsonaazụ SARS-CoV-2 mRNA na ọgwụ mgbochi ọdịnala.E jiri ya tụnyere ọgwụ mgbochi protein recombinant: ọgwụ mgbochi mRNA dị elu karịa ọgwụ mgbochi protein na nzaghachi germinal center, Tfh activation, neutralizing antibody production, sel B ebe nchekwa kpọmkwem, na sel plasma dị ogologo ndụ [11].

Mgbe ahụ, ka ndị na-achọ ọgwụ mgbochi SARS-CoV-2 mRNA batara n'ule ụlọ ọgwụ, ewelitere nchegbu banyere obere oge nchebe ọgwụ mgbochi.Ndị ọkà mmụta sayensị ewepụtala ụdị ọgwụ mgbochi mRNA mebere nucleoside nke a na-akpọ mRNA-RBD.Otu ntụtụ nwere ike iwepụta ọgwụ mgbochi mgbochi siri ike na nzaghachi cellular, yana ọ nwere ike ichebe oke oke ụdị bu ọrịa 2019-nCoV, yana ọkwa mgbochi mgbochi dị elu nke edobere ma ọ dịkarịa ala ọnwa 6.5.Ihe omuma a na-egosi na otu dose nke mRNA-RBD na-enye nchebe ogologo oge megide ihe ịma aka SARS-CoV-2 [12].
Enwekwara ndị sayensị na-arụ ọrụ iji mepụta ọgwụ mgbochi ọhụrụ dị mma ma dị irè megide COVID-19, dị ka ọgwụ mgbochi BNT162b.Macaques echedoro site na SARS-CoV-2, chebe traktị iku ume ala site na nje virus RNA, mepụta ọgwụ mgbochi siri ike, na egosighi akara ọ bụla nke nkwalite ọrịa.A na-enyocha ndị na-eme ntuli aka abụọ ugbu a na ule nke Mbụ nke Mbụ, na nyocha na ule zuru ụwa ọnụ II/III na-agakwa n'ihu, na ngwa dị nso n'akụkụ [13].

05
Ọkwa ọgwụ mgbochi mRNA n'ụwa

Ka ọ dị ugbu a, a maara BioNTech, Moderna na CureVac dị ka ndị isi atọ kachasị elu n'ụwa.N'ime ha, BioNTech na Moderna bụ ndị na-ebute ụzọ na nyocha na mmepe nke ọgwụ mgbochi okpueze ọhụrụ.Moderna anọwo na-elekwasị anya na nyocha na mmepe nke ọgwụ na ọgwụ mgbochi mRNA metụtara.Ọgwụ mgbochi COVID-19 nke III nke mRNA-1273 bụ ọrụ ụlọ ọrụ na-eto ngwa ngwa.BioNTech bụkwa ụlọ ọrụ nyocha na mmepe ọgwụ mRNA na-eduga n'ụwa, yana mkpokọta ọgwụ / ịgba ọgwụ mgbochi 19 mRNA, 7 n'ime ha abanyela na ọkwa ụlọ ọgwụ.CureVac nọ na-elekwasị anya na nyocha na mmepe nke ọgwụ / ịgba ọgwụ mgbochi mRNA, ọ bụkwa ụlọ ọrụ mbụ n'ụwa iji guzobe usoro mmepụta RNA GMP kwadoro, na-elekwasị anya na etuto ahụ, ọrịa na-efe efe na ọrịa na-adịghị ahụkebe.

Ngwaahịa ndị emetụtara:Ihe mgbochi RNase
Okwu ndị dị mkpa: ọgwụ mgbochi miRNA, RNA Isolation, mmịpụta RNA, ihe mgbochi RNase

Ntụaka:1.K Karikó, Buckstein M, Ni H, et al.Mwepu nke nnabata RNA site na ndị na-anabata ihe dị ka Toll: Mmetụta nke mgbanwe Nucleoside na mmalite mmalite nke RNA[J].Mgbochi, 2005, 23 (2): 165-175 .
2. K Karikó, Muramatsu H , Welsh FA , et al.Ntinye nke Pseudouridine n'ime mRNA Na-enweta Vector Nonimmunogenic Kachasị Elu Site n'Ike Ntụgharị Asụsụ na Nkwụsi Ike Nnụnụ[J].Usoro ọgwụgwọ anụ ahụ, 2008.3.Chonn A, Cullis PR.Ọganihu na nso nso a na teknụzụ liposome na ngwa ha maka nnyefe mkpụrụ ndụ sistemu[J].Nlebanya nnyefe ọgwụ dị elu, 1998, 30 (1-3): 73.4.Kulkarni JA, Witzigmann D, Chen S, et al.Nkà na ụzụ Lipid Nanoparticle maka Nsụgharị Clinical nke siRNA Therapeutics[J].Akaụntụ nke Nnyocha Chemical, 2019, 52(9.5.Kariko, Katalin, Madden, et al.Ngosipụta kinetics nke mRNA nucleoside-gbanwetụrụ na-ebunye n'ime nanoparticles lipid na ụmụ oke site n'ụzọ dị iche iche[J].Akwụkwọ akụkọ nke Mwepụta Achịkwa Official Journal of the Controlled Release Society, 2015.6.Nchekwa nje Zika site na otu obere ọgwụ mgbochi nucleoside meziri mRNA [J].Ọdịdị, 2017, 543 (7644): 248-251.7 .Pardi N , Secreto AJ , Shan X , et al.Nlekọta nke mRNA mezigharịrị nucleoside nke na-edobe ihe mgbochi mgbochi na-echebe ụmụ oke mmadụ site na ịma aka HIV-1[J].Nkwukọrịta okike, 2017, 8:14630.8.Stadler CR, B?Hr-Mahmud H , Celik L , et al.Mwepu nke nnukwu etuto dị na ụmụ oke site na ọgwụ mgbochi bispecific nke mRNA nwere koodu[J].Ọgwụ okike, 2017.9.NN Zhang, Li XF, Deng YQ, et al.Ogwu mRNA nke nwere ike ikpo ọkụ megide COVID-19[J].Cell, 2020.10.D Laczkó, Hogan MJ, Toulmin SA, et al.Otu ogwu mgbochi na Nucleoside-gbanwechara mRNA Vaccines na-ewepụ nzaghachi cellular siri ike na ihu ọchị megide SARS-CoV-2 na ụmụ oke - ScienceDirect[J].2020.11.Lederer K , Castao D , Atria DG , et al.Ọgwụ mgbochi SARS-CoV-2 mRNA na-akwalite nzaghachi Center nke Antigen-Specific Germinal nke jikọtara ya na Ọgbọ mgbochi mgbochi mmadụ[J].Mgbochi, 2020, 53 (6): 1281-1295.e5.12.Huang Q, Ji K, Tian S, et al.Ogwu mRNA nke otu dose na-enye nchebe ogologo oge maka ụmụ oke transgenic hACE2 sitere na SARS-CoV-2[J].Nkwukọrịta okike.13.Vogel AB, Kanevsky I, Ye C, et al.Ọgwụ mgbochi BNT162b na-echebe rhesus macaques site na SARS-CoV-2[J].okike, 2021:1-10 .


Oge nzipu: Jun-20-2022