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Hōʻike pinepine ʻia ka hana o ka hana ʻana i ke kano he mea mahalo ʻole. Ma ka ʻōlelo a Bill Foege, kekahi o nā kauka olakino maikaʻi loa o ka honua, "ʻAʻohe mea e mahalo iā ʻoe no ka hoʻopakele ʻana iā lākou mai kahi maʻi a lākou i ʻike ʻole ai."

Akā ke kūʻē nei nā kauka olakino olakino he kiʻekiʻe loa ka hoʻihoʻi ʻana i ka hoʻopukapuka no ka mea ke pale aku nei nā lāʻau lapaʻau i ka make a me ke kīnā, ʻoi loa no nā keiki. No laila, no ke aha mākou e hana ʻole ai i nā lāʻau lapaʻau no nā maʻi hiki ke pale ʻia i ke kano? ʻO ke kumu he pono a palekana ka lāʻau lapaʻau i hiki ke hoʻohana ʻia i nā poʻe olakino, kahi e lōʻihi a paʻakikī ke kaʻina hana o ka hoʻomohala ʻana.

Ma mua o 2020, ʻo ka manawa awelika mai ka hoʻomaka mua ʻana a hiki i ka laikini ʻana i nā lāʻau lapaʻau he 10 a 15 mau makahiki, me ka manawa pōkole loa he ʻehā makahiki (mump vaccine). ʻO ka hoʻomohala ʻana i kahi kano COVID-19 i loko o 11 mau mahina he hana kupaianaha ia, i hana ʻia e nā makahiki o ka noiʻi kumu ma nā kahua kano hou, ʻo ka mRNA kaulana loa. Ma waena o lākou, he mea koʻikoʻi nā haʻawina a Drew Weissman a me Kauka Katalin Kariko, nā mea i loaʻa i ka 2021 Lasker Clinical Medical Research Award.

Hoʻokumu ʻia ka loina ma hope o nā lāʻau lapaʻau nucleic acid i ke kānāwai koʻikoʻi o Watson lāua ʻo Crick e unuhi ʻia ka DNA i mRNA, a ua unuhi ʻia ka mRNA i nā protein. Ma kahi kokoke i 30 mau makahiki i hala aku nei, ua hōʻike ʻia ka hoʻokomo ʻana i ka DNA a i ʻole mRNA i loko o ke kelepona a i ʻole kekahi mea ola e hōʻike i nā protein i hoʻoholo ʻia e nā kaʻina nucleic acid. Ma hope koke iho, ua hōʻoia ʻia ka manaʻo kano nucleic acid ma hope o ka hōʻike ʻia ʻana o nā protein i hōʻike ʻia e ka DNA exogenous e hoʻoulu i kahi pane pale pale. Eia nō naʻe, ua kaupalena ʻia ka hoʻohana ʻana i nā lāʻau lapaʻau DNA maoli, ma mua o nā hopohopo palekana e pili ana i ka hoʻohui ʻana i ka DNA i loko o ka genome kanaka, a ma hope no ka paʻakikī o ka hoʻonui ʻana i ka lawe ʻana i ka DNA i loko o ka nucleus.

ʻO ka ʻokoʻa, ʻo ka mRNA, ʻoiai hiki ke maʻalahi i ka hydrolysis, ʻoi aku ka maʻalahi o ka hana ʻana no ka hana ʻana o ka mRNA i loko o ka cytoplasm a no laila ʻaʻole pono e hoʻopuka i nā waikawa nucleic i loko o ka nucleus. He mau makahiki o ka noiʻi kumu a Weissman lāua ʻo Kariko, i ka hoʻomaka ʻana i kā lākou lab ponoʻī a ma hope ma hope o ka laikini ʻana i ʻelua mau ʻoihana biotechnology (Moderna a me BioNTech), alakaʻi i kahi kano mRNA i lilo i mea maoli. He aha ke kī i ko lākou holomua?

Ua lanakila lākou i kekahi mau pilikia. ʻIke ʻia ka mRNA e nā mea hoʻokipa hoʻomaopopo i ke ʻano o ka ʻōnaehana pale (FIG. 1), me nā lālā o ka ʻohana Toll-like receptor (TLR3 a me TLR7/8, ka manaʻo o ka RNA kaulua a me ka RNA hoʻokahi, kēlā me kēia) a me ka waika retinoic e hoʻoulu i ke ala o ka gene I protein (RIG-1), ka mea e hoʻoulu ai i ka mumū a me ke ʻano o ka cell recognition (RIG-1). Hoʻomaopopo i ka RNA pōkole kaulua a hoʻāla i ka interferon ʻano I, a laila hoʻāla i ka ʻōnaehana immune adaptive). No laila, hiki i ka hoʻokomo ʻana i ka mRNA i loko o nā holoholona ke haʻalulu, me ka manaʻo e kaupalena ʻia ka nui o ka mRNA i hiki ke hoʻohana ʻia i nā kānaka i mea e pale ai i nā hopena ʻaoʻao ʻae ʻole.

No ka ʻimi ʻana i nā ala e hōʻemi ai i ka mumū, ua hoʻomaka ʻo Weissman lāua ʻo Kariko e hoʻomaopopo i ke ʻano o ka hoʻokaʻawale ʻana o nā mea hoʻokipa hoʻohālike ma waena o RNA i loaʻa i ka pathogen a me kā lākou RNA ponoʻī. Ua ʻike lākou he nui nā Rnas intracellular, e like me ka Rnas ribosomal waiwai, i hoʻololi nui ʻia a manaʻo ʻia ua ʻae kēia mau hoʻololi i kā lākou mau Rnas e pakele i ka ʻike kūlohelohe.

Ua hōʻike ʻo Weissman lāua ʻo Kariko i ka hoʻololi ʻana i ka mRNA me ka pseudouridine ma kahi o ka ouridine i hōʻemi i ka hoʻoulu ʻana o ka immune ʻoiai e paʻa ana ka hiki ke hoʻopili i nā protein. Hoʻonui kēia hoʻololi i ka hana protein, a hiki i ka 1,000 manawa o ka mRNA i hoʻololi ʻole ʻia, no ka mea, ʻaʻole ʻike ʻia ka mRNA i hoʻololi ʻia e ka protein kinase R (kahi mea ʻike e ʻike ai i ka RNA a laila phosphorylates a hoʻāla i ka mea hoʻomaka unuhi eIF-2α, a laila e pani i ka unuhi protein). ʻO ka mRNA i hoʻololi ʻia ʻo Pseudouridine ka iwi kuamoʻo o nā lāʻau lapaʻau mRNA i hoʻomohala ʻia e Moderna a me Pfizer-Biontech.

ʻO ka hopena hope loa e hoʻoholo ai i ke ala maikaʻi loa e hoʻopili ai i ka mRNA me ka ʻole o ka hydrolysis a me ke ala maikaʻi loa e hoʻopuka ai i loko o ka cytoplasm. Ua hoʻāʻo ʻia nā hana mRNA he nui i nā ʻano lāʻau lapaʻau e kūʻē i nā maʻi ʻē aʻe. I ka makahiki 2017, ua hōʻike ʻia nā hōʻike lapaʻau mai ia mau hoʻāʻo ʻana i ka encapsulation a me ka hāʻawi ʻana i nā lāʻau lapaʻau mRNA me nā nanoparticles lipid i hoʻonui i ka immunogenicity ʻoiai e mālama ana i kahi ʻaoʻao palekana.

ʻO ke kākoʻo ʻana i nā haʻawina i nā holoholona ua hōʻike ʻia ʻo ka lipid nanoparticles e kuhikuhi ana i nā cell antigen-presenting i ka hoʻoheheʻe ʻana i nā ʻōpū lymph a kōkua i ka pane ma o ka hoʻoulu ʻana i nā ʻano kikoʻī o nā pūnaewele T kōkua follicular CD4. Hiki i kēia mau pūnaewele T ke hoʻonui i ka hana antibody, ka helu o nā cell plasma lōʻihi a me ke kiʻekiʻe o ka pane ʻana o ka cell B makua. Hoʻohana ʻia nā lāʻau lapaʻau ʻelua ma COVID-19 mRNA i kēia manawa i nā formulations lipid nanoparticle.

ʻO ka mea pōmaikaʻi, ua hana ʻia kēia mau holomua i ka noiʻi kumu ma mua o ka maʻi maʻi, e ʻae ana i nā hui lāʻau lapaʻau e kūkulu i kā lākou kūleʻa. He palekana, maikaʻi a hana nui ʻia nā lāʻau lapaʻau mRNA. ʻOi aku ma mua o 1 biliona mau kano o ka maʻi maʻi mRNA i lawelawe ʻia, a ʻo ka hoʻonui ʻana i ka hana i 2-4 biliona mau kaona i 2021 a me 2022 e koʻikoʻi i ka hakakā honua me COVID-19. ʻO ka mea pōʻino, he nui nā mea like ʻole i ka loaʻa ʻana o kēia mau mea hana ola, me nā lāʻau lapaʻau mRNA i kēia manawa e lawelawe nui ʻia ma nā ʻāina kiʻekiʻe; A hiki i ka hiki ʻana o ka hana kano i kona kiʻekiʻe, e mau ana ka like ʻole.

ʻOi aku ka laulā, hoʻohiki ʻo mRNA i ka wanaʻao hou i ke kahua o ka vaccinology, e hāʻawi iā mākou i ka manawa e pale aku ai i nā maʻi ʻē aʻe, e like me ka hoʻomaikaʻi ʻana i nā maʻi maʻi flu, a me ka hoʻomohala ʻana i nā lāʻau lapaʻau no nā maʻi e like me ka maʻi maʻi e like me ka maʻi maʻi, HIV, a me ka maʻi maʻi e pepehi i ka nui o nā maʻi a ʻaʻole kūpono i nā ʻano hana maʻamau. ʻO nā maʻi e like me ka maʻi kanesa, i manaʻo ʻia ma mua he paʻakikī ke mālama ʻia ma muli o ka liʻiliʻi o ka hoʻomohala ʻana i ka maʻi maʻi a me ka pono o nā lāʻau lapaʻau pilikino, hiki ke noʻonoʻo ʻia i kēia manawa no ka hoʻomohala ʻana i nā kano. ʻAʻole pili wale ka mRNA i nā kano. ʻO nā piliona o ka mRNA a mākou i hoʻokomo ai i nā maʻi a hiki i kēia lā ua hōʻoia i ko lākou palekana, e wehe ana i ke ala no nā lāʻau lapaʻau RNA ʻē aʻe e like me ka hoʻololi ʻana i ka protein, RNA interference, a me CRISPR-Cas (nā pūʻulu maʻamau o interspaced short palindromic repeats and related Cas endonucrenases) gene editing. Ua hoʻomaka ka hoʻololi RNA.

Ua hoʻopakele nā ​​hana ʻepekema ʻo Weissman lāua ʻo Kariko i nā miliona o nā ola, a ke neʻe nei ka huakaʻi ʻoihana a Kariko, ʻaʻole no ka mea ʻokoʻa, akā no ka mea āpau. He kamaʻāina ʻo ia mai kahi ʻāina ʻEulopa Hikina, ua neʻe ʻo ia i ʻAmelika Hui Pū ʻIa e alualu i kāna mau moeʻuhane ʻepekema, e hakakā wale me ka ʻōnaehana ʻoihana US, nā makahiki o ke kālā noiʻi paʻakikī, a me ka hoʻohaʻahaʻa ʻana. Ua ʻae ʻo ia e ʻoki i ka uku no ka holo ʻana o ka lab a hoʻomau i kāna noiʻi. He mea paʻakikī ka huakaʻi ʻepekema a Kariko, kahi i ʻike ʻia e ka nui o nā wahine, nā malihini a me nā mea liʻiliʻi e hana ana ma ke kula. Inā ua laki ʻoe i ka hālāwai ʻana me Kauka Kariko, ʻo ia ke ʻano o ka haʻahaʻa; ʻO ia paha ka paʻakikī o kona wā i hala.

ʻO ka hana paʻakikī a me nā hoʻokō nui a Weissman lāua ʻo Kariko e hōʻike ana i kēlā me kēia ʻano o ka hana ʻepekema. ʻAʻohe kapuaʻi, ʻaʻohe mile. He lōʻihi a paʻakikī kā lākou hana, pono ke kūpaʻa, ka naʻauao a me ka ʻike. ʻOiai ʻaʻole pono mākou e poina i ka nui o ka poʻe a puni ka honua ʻaʻole i loaʻa i nā lāʻau lapaʻau, ʻo ka poʻe o mākou e pōmaikaʻi i ka loaʻa ʻana o ka maʻi COVID-19, mahalo lākou no nā pono palekana o nā kano. Hoʻomaikaʻi ʻia i ʻelua mau ʻepekema kumu i hoʻokō ʻia ka hana koʻikoʻi i nā kano mRNA. Hui pū wau me nā mea ʻē aʻe he nui i ka hōʻike ʻana i koʻu mahalo pau ʻole iā lākou.