Inkomoko: WuXi AppTec

Imyaka yashize, murwego rwo kuvura RNA rwerekanye ibintu biturika-mu myaka 5 ishize yonyine, imiti 11 ya RNA yemejwe na FDA, ndetse uyu mubare urenze umubare w’ubuvuzi bwa RNA bwemewe mbere!Ugereranije nubuvuzi gakondo, ubuvuzi bwa RNA burashobora guteza imbere ubuvuzi bwihuse hamwe nigipimo kinini cyo gutsinda mugihe cyose gene ikurikiranye intego izwi.Ku rundi ruhande, imiti myinshi ya RNA iracyaboneka gusa mu kuvura indwara zidasanzwe, kandi iterambere ry’ubwo buvuzi riracyafite imbogamizi nyinshi mu bijyanye no kuvura igihe kirekire, umutekano, no gutanga.Mu kiganiro cy'uyu munsi ,.itsinda ryibirimo rya WuXi AppTec rizasuzuma iterambere murwego rwo kuvura RNA mumwaka ushize, kandi dutegereje ejo hazaza h'iki gice kigaragara hamwe nabasomyi.

▲ 11 Ubuvuzi bwa RNA cyangwa inkingo byemejwe na FDA mu myaka 5 ishize

Kuva ku ndwara zidasanzwe kugeza ku ndwara zisanzwe, indabyo nyinshi zirabya

Mu cyorezo gishya cy'ikamba, urukingo rwa mRNA rwavutse nta handi kandi rwitabiriwe cyane n'inganda.Nyuma yaintambwe mu iterambere ry’inkingo z’indwara zandura, indi mbogamizi ikomeye ihura n’ikoranabuhanga rya mRNA ni kwagura uburyo bwo kuvura no gukumira indwara nyinshi.
Muri bo,Urukingo rwa kanseri yihariye ni urwego rwingenzi rwo gukoresha ikoranabuhanga rya mRNA, kandi twabonye ibisubizo byiza byubuvuzi byinkingo nyinshi za kanseri uyumwaka.Muri uku kwezi gusa, urukingo rwa kanseri rwihariye rwateguwe na Moderna na Merck, hamwe na PD-1 inhibitor Keytruda,yagabanije ingarukabyo kwisubiramo cyangwa gupfa ku barwayi bafite icyiciro cya III na IV melanoma nyuma yo kuvura ibibyimba burundu kuri 44% (ugereranije na Keytruda monotherapy).Itangazo rigenewe abanyamakuru ryerekanye ko ari ubwa mbere urukingo rwa kanseri ya mRNA rugaragaza akamaro mu kuvura melanoma mu isuzuma ry’amavuriro ryateganijwe, kikaba ari ikintu cy’ingenzi mu iterambere ry’inkingo za kanseri ya mRNA.
Byongeye kandi, inkingo za mRNA zirashobora kandi kongera ingaruka zo kuvura ingirabuzimafatizo.Kurugero, ubushakashatsi bwakozwe na BioNTech bwerekanye ko niba abarwayi babanje gushiramo imiti mike ya CLDN6 igamije CAR-T ivuraBNT211, hanyuma bagaterwa urukingo rwa mRNA rurimo CLDN6, barashobora gukangura selile CAR-T muri vivo bagaragaza CLDN6 hejuru ya selile zitanga antigen.Kwiyongera, bityo bikazamura ingaruka za anticancer.Ibisubizo by'ibanze byerekanye ko abarwayi 4 kuri 5 bahawe imiti ivura bageze ku gisubizo, cyangwa 80%.

Usibye kuvura mRNA, kuvura oligonucleotide hamwe nubuvuzi bwa RNAi byageze no ku musaruro mwiza mu kwagura indwara.Mu kuvura indwara ya hepatite B idakira, abarwayi bagera kuri 30% ntibashobora kumenya antigen ya hepatite B na virusi ya hepatite B muri vivo nyuma yo gukoresha antisense oligonucleotide ivurabepirovirsen yafatanije na GSK na Ionisibyumweru 24.Mu barwayi bamwe, ndetse n'ibyumweru 24 nyuma yo guhagarika imiti, ibyo bimenyetso bya hepatite B byari bitaramenyekana mu mubiri.
Ku bw'amahirwe, imiti ya RNAiVIR-2218 yatejwe imbere na Vir Biotechnology na Alnylam yarahujwehamwe na interferon α, no mu cyiciro cya 2 cy’amavuriro, abagera kuri 30% by’abarwayi ba hepatite B idakira na bo ntibashoboye kumenya antigen yo mu bwoko bwa hepatite B (HBsAg).Byongeye kandi, aba barwayi bakoze antibodies zirwanya poroteyine ya hepatite B, byerekana uburyo bwiza bwo kwirinda indwara.Ufatiye hamwe ibisubizo, inganda zerekana ko kuvura RNA bishobora kuba urufunguzo rwo gukiza indwara ya hepatite B.
Iyi ishobora kuba intangiriro yubuvuzi bwa RNA bwindwara zisanzwe.Nk’uko umuyoboro wa R&D wa Alnylam ubitangaza, urategura kandi imiti ya RNAi yo kuvura hypertension, indwara ya Alzheimer, ndetse na steatohepatite idafite inzoga, kandi ejo hazaza hakwiye gutegereza.

Kumena icyuho cyo gutanga RNA ivura

Gutanga imiti ya RNA nimwe mubibuza kugabanya ikoreshwa ryayo.Abahanga kandi barimo guteza imbere tekinoloji zitandukanye kugirango batange imiti ya RNA mu ngingo no mu ngingo zitari umwijima.
Bumwe mu buryo bushoboka ni "guhuza" imiti ivura RNA hamwe na molekile yihariye.Kurugero, Avidity Biosciences iherutse gutangaza ko urubuga rwikoranabuhanga rushobora guhuza antibodiyite za monoclonal na oligonucleotide kuriguhuza neza siRNAs.yoherejwe kumitsi ya skeletale.Itangazo rigenewe abanyamakuru ryerekanye ko ari ubwa mbere siRNA ishobora kwibasirwa neza kandi igashyikirizwa imitsi y’umuntu, iyi ikaba ari intambwe ikomeye mu rwego rwo kuvura RNA.

Inkomoko y'amashusho: 123RF

Usibye tekinoroji ya antibody conjugation, ibigo byinshi biteza imbere lipide nanoparticles (LNP) nabyo "bizamura" abatwara ibintu.Kurugero, Ubuvuzi bwa ReCodeikoresha uburyo bwihariye bwo Guhitamo Intego ya LNP Ikoranabuhanga (SORT) kugirango itange ubwoko butandukanye bwubuvuzi bwa RNA mubihaha, impyiko, umwijima nizindi ngingo.Muri uyu mwaka, isosiyete yatangaje ko irangiye miliyoni 200 z’amadolari y’Amerika yo gutera inkunga Series B, hamwe n’ishami ry’imari shoramari rya Pfizer, Bayer, Amgen, Sanofi n’andi masosiyete akomeye y’imiti yitabira ishoramari.Kernal Biologics, nayo yakiriye miliyoni 25 z'amadolari mu gutera inkunga Series A muri uyu mwaka, irategura kandi LNPs idakusanyiriza mu mwijima, ariko ishobora kugeza mRNA ku ngirabuzimafatizo nk'ubwonko cyangwa ibibyimba byihariye.
Orbital Therapeutics, yatangijwe muri uyu mwaka, nayo ifata itangwa rya RNA nkicyerekezo cyingenzi cyiterambere.Muguhuza tekinoroji ya RNA nuburyo bwo gutanga, isosiyete iteganya kubaka urubuga rwihariye rwa tekinoroji ya RNA rushobora kwongerera imbaraga nubuzima bwa kabiri bwo kuvura udushya twa RNA no kubigeza ku bwoko butandukanye bwingirabuzimafatizo zitandukanye.

Ubwoko bushya bwa RNA ivura bugaragara mugihe cyamateka

Kugeza ku ya 21 Ukuboza uyu mwaka, mu rwego rwo kuvura RNA, habaye ibikorwa 31 byo gutera inkunga hakiri kare (reba uburyo bukoreshwa mu mpera z’ingingo kugira ngo ubone ibisobanuro birambuye), birimo amasosiyete 30 akomeye (isosiyete imwe yakiriye inkunga inshuro ebyiri), yose hamwe akaba angana na miliyari 1.74 z'amadolari y'Amerika.Isesengura ry’ibi bigo ryerekana ko abashoramari bafite icyizere kuri ayo masosiyete akomeye ateganijwe gukemura ibibazo byinshi by’ubuvuzi bwa RNA, kugira ngo bamenye neza ubushobozi bwo kuvura RNA no kugirira akamaro abarwayi benshi.
Hariho ibigo bizamuka kandi biza biteza imbere ubwoko bushya bwa RNA bwo kuvura.Bitandukanye na oligonucleotide gakondo, RNAi cyangwa mRNA, ubwoko bushya bwa molekile ya RNA yakozwe naya masosiyete biteganijwe ko izacamo icyuho cyubuvuzi buriho.
Kuzenguruka RNA ni hamwe mu hantu hashyushye mu nganda.Ugereranije n'umurongo wa mRNA, tekinoroji ya RNA izenguruka yakozwe na sosiyete igezweho yitwa Orna Therapeutics irashobora kwirinda kumenyekana na sisitemu y’umubiri yavukanye ndetse na exonuclease, ibyo ntibigabanya cyane ubudahangarwa bw'umubiri, ariko kandi bifite umutekano muke.Byongeye kandi, ugereranije numurongo wa RNA, guhinduranya kuzenguruka kwa RNA kuzenguruka ni ntoya, kandi RNA izenguruka irashobora kwishyiriraho LNP imwe, bikazamura uburyo bwo gutanga imiti ya RNA.Ibiranga bishobora gufasha kunoza imbaraga nigihe kirekire cyo kuvura RNA.
Uyu mwaka, isosiyete yarangije miliyoni 221 zamadorali y’Amerika mu cyiciro cya B cyiciro cyo gutera inkunga, inagera no mu bushakashatsi kandiubufatanye bwiterambere hamwe na Merck agera kuri miliyari 3,5 US $.Mubyongeyeho, Orna ikoresha kandi uruziga RNA kugirango itange ubuvuzi bwa CAR-T mu nyamaswa, yuzuza ibimenyetso byaigitekerezo.
Usibye kuzenguruka RNA, tekinoroji ya mRNA (samRNAs) yongerewe inkunga nabashoramari.Iri koranabuhanga rishingiye ku buryo bwo kwongera imbaraga za virusi ya RNA, zishobora gutuma habaho kwigana urutonde rwa samRNA muri cytoplazme, bikongerera imvugo imvugo ya mRNA ivura, bityo bikagabanya inshuro z’ubuyobozi.Ugereranije n'umurongo gakondo mRNA, samRNA irashobora kugumana urugero rwa poroteyine igereranya inshuro zigera ku 10 munsi.Uyu mwaka, RNAimmune, yibanda ku iterambere ry’uru rwego, yakiriye miliyoni 27 z’amadolari y’Amerika mu gutera inkunga Series A.
tekinoroji ya tRNA nayo ikwiye gutegereza.Ubuvuzi bushingiye kuri tRNA burashobora "kwirengagiza" guhagarika codon itari yo mugihe selile ikora proteine, kugirango proteine ​​isanzwe yuzuye yuzuye.Kuberako hari ubwoko buke cyane bwo guhagarika codons kuruta indwara zifitanye isano, ubuvuzi bwa tRNA bufite ubushobozi bwo gukora imiti imwe ishobora kuvura indwara nyinshi.Uyu mwaka, hC Bioscience yibanda ku buvuzi bwa tRNA, yakusanyije miliyoni 40 z'amadorali y'Amerika mu gutera inkunga Series A.

Epilogue

Nuburyo bugaragara bwo kuvura, RNA ivura yageze ku iterambere ryihuse mumyaka yashize, kandi imiti myinshi yaremewe.Duhereye ku majyambere agezweho mu nganda, birashobora kugaragara ko ubuvuzi bwa RNA bugenda bwagura indwara zitandukanye ubwo buvuzi bushobora kuvura, gutsinda inzitizi zitandukanye mu gutanga intego, no guteza imbere molekile nshya ya RNA kugira ngo tuneshe imbogamizi z’ubuvuzi buriho mu bijyanye no gukora neza no kuramba.ibibazo byinshi.Muri iki gihe gishya cyo kuvura RNA, aya masosiyete akomeye arashobora kuba intandaro yinganda mumyaka mike iri imbere.

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