Umthombo: WuXi AppTec

Kwiminyaka yamva nje, icandelo lonyango lwe-RNA libonise indlela eqhumayo-kule minyaka mi-5 idlulileyo iyodwa, kuye kwavunywa unyango lwe-RNA eli-11 yi-FDA, kwaye eli nani lide ligqithe isixa sonyango lwe-RNA olwaluvunyiwe ngaphambili!Xa kuthelekiswa nonyango lwendabuko, unyango lwe-RNA lunokuphuhlisa ngokukhawuleza unyango olujoliswe kuyo kunye nezinga eliphezulu lempumelelo ukuba nje ukulandelelana kwemfuza ekujoliswe kuyo kuyaziwa.Kwelinye icala, uninzi lwezonyango ze-RNA zisafumaneka kuphela ukunyanga izifo ezinqabileyo, kwaye uphuhliso lwezo zonyango lusajongene nemingeni emininzi ngokwemigaqo yokuqina konyango, ukhuseleko kunye nokuhanjiswa.Kwinqaku lanamhlanje, iIqela lomxholo weWuXi AppTec liza kuphonononga inkqubela kwicandelo lonyango lwe-RNA kulo nyaka uphelileyo, kwaye lijonge phambili kwikamva lalo mmandla uvelayo kunye nabafundi.

▲ I-11 zonyango lwe-RNA okanye izitofu zivunyiwe yi-FDA kule minyaka mihlanu idlulileyo.

Ukususela kwizifo ezinqabileyo ukuya kwizifo eziqhelekileyo, iintyatyambo ezininzi ziyaqhakaza

Kubhubhani omtsha wesithsaba, isitofu sokugonya se-mRNA sazalwa ngaphandle kwendawo kwaye sifumene ingqwalasela ebanzi kushishino.Emva kweimpumelelo kuphuhliso lwezitofu zokugonya izifo ezosulelayo, omnye umceli mngeni omkhulu ojongene nobuchwephesha be-mRNA kukwandisa umda wesicelo sonyango kunye nothintelo lwezifo ezininzi.
Phakathi kwabo,izitofu zokugonya zomhlaza ezizimeleyo ziyinxalenye ebalulekileyo yetekhnoloji ye-mRNA, kwaye sibone iziphumo ezincumisayo zeklinikhi zezitofu ezininzi zomhlaza kulo nyaka.Kule nyanga nje, iyeza lokugonya umhlaza lomntu ngamnye liphuhliswe ngokudibeneyo yiModerna kunye neMerck, kudityaniswe ne-PD-1 inhibitor Keytruda,yanciphisa umngciphekoukuphindaphinda okanye ukufa kwizigulane ezinesigaba se-III kunye ne-IV ye-melanoma emva kokutshatyalaliswa okupheleleyo kwe-tumor nge-44% (xa kuthelekiswa ne-Keytruda monotherapy).Ushicilelo lweendaba lwabonisa ukuba esi sisihlandlo sokuqala ukuba isitofu sokugonya somhlaza we-mRNA sibonise ukusebenza kakuhle kunyango lwe-melanoma kulingo lwezonyango olungacwangciswanga, esisisiganeko esibalulekileyo ekuphuhlisweni kogonyo lomhlaza we-mRNA.
Ukongeza, izitofu zokugonya ze-mRNA zinokuphucula isiphumo sonyango lweseli.Ngokomzekelo, uphando olwenziwa yi-BioNTech lubonise ukuba ukuba izigulane zifakwe kuqala ngedosi ephantsi ye-CLDN6 ejoliswe kunyango lwe-CAR-T.BNT211, kwaye emva koko ifakwe nge-mRNA yokugonya i-CLDN6, inokuvuselela iiseli ze-CAR-T kwi-vivo ngokubonisa i-CLDN6 kumphezulu weeseli ze-antigen-presenting.Ukwandisa, ngaloo ndlela kuphuculwa umphumo we-anticancer.Iziphumo zangaphambili zibonise ukuba izigulane ezi-4 kwezi-5 ezifumene unyango oludibeneyo zifumene impendulo engaphelelanga, okanye i-80%.

Ukongeza kunyango lwe-mRNA, unyango lwe-oligonucleotide kunye nonyango lwe-RNAi lufumene iziphumo ezilungileyo ekwandiseni umda wezifo.Kunyango lwe-hepatitis B engapheliyo, phantse i-30% yezigulana azikwazi ukubona i-antigen ye-hepatitis B kunye ne-virus ye-hepatitis B ye-DNA kwi-vivo emva kokusebenzisa unyango lwe-oligonucleotide.i-bepirovirsen iphuhliswe ngokudibeneyo yi-GSK kunye ne-Ionisiiveki ezingama-24.Kwezinye izigulana, kwiiveki ezingama-24 emva kokuyeka unyango, ezi ziphawuli ze-hepatitis B zazingekabonakali emzimbeni.
Ngokuzenzekelayo, unyango lwe-RNAiI-VIR-2218 iphuhliswe ngokudibeneyo yi-Vir Biotechnology kunye ne-Alnylam yadityaniswakunye ne-interferon α, kunye nezilingo zekliniki zesigaba se-2, malunga ne-30% yezigulane ezingapheliyo ze-hepatitis B nazo zahluleka ukufumana i-antigen ye-hepatitis B ebusweni (HBsAg).Ukongezelela, ezi zigulana zenze amajoni omzimba achasene neprotheyini ye-hepatitis B, ebonisa impendulo echanekileyo yokuzikhusela komzimba.Ukuthatha ezi ziphumo kunye, ishishini libonisa ukuba unyango lwe-RNA lunokuba ngundoqo kunyango olusebenzayo lwe-hepatitis B.
Oku kunokuba sisiqalo nje sonyango lwe-RNA kwizifo eziqhelekileyo.Ngokutsho kombhobho we-R&D we-Alnylam, ikwaphuhlisa amayeza e-RNAi onyango lwe-hypertension, isifo se-Alzheimer, kunye ne-non-alcoholic steatohepatitis, kwaye ikamva lifanele ukujongwa kulo.

Ukophula umqobo wonikezelo lonyango lwe-RNA

Ukunikezelwa konyango lwe-RNA yenye yezinto ezithintela ukusetyenziswa kwayo.Izazinzulu zikwaphuhlisa ubuchwephesha obahlukeneyo ukuhambisa ngokuthe ngqo unyango lwe-RNA kumalungu kunye nezicubu ezingaphandle kwesibindi.
Enye yeendlela ezinokuthi "zibophe" ii-RNA zonyango kunye neemolekyuli ezithe ngqo kwizicubu .Umzekelo, i-Avidity Biosciences isandula ukubhengeza ukuba iqonga layo letekhnoloji linokudibanisa amajoni omzimba we-monoclonal kwi-oligonucleotides.zibophelela ngokufanelekileyo ii-siRNAs.ithunyelwe kwisihlunu samathambo.Ushicilelo lweendaba lubonise ukuba eli lixesha lokuqala lokuba i-siRNA inokujoliswa ngempumelelo kwaye ihanjiswe kwizicubu zomzimba zomntu, eyona nto iyimpumelelo enkulu kwintsimi yonyango lwe-RNA.

Umthombo womfanekiso: 123RF

Ukongeza kwitekhnoloji ye-antibody conjugation, inani leenkampani eziphuhlisa i-lipid nanoparticles (LNP) nazo "ziphucula" abathwali abanjalo.Umzekelo, ReCode Therapeuticisebenzisa i-Selective Organ Targeting LNP Technology (SORT) ekhethekileyo yokubonelela ngeendlela ezahlukeneyo zonyango lwe-RNA kwimiphunga, i-spleen, isibindi kunye nezinye izitho.Kulo nyaka, inkampani ibhengeze ukugqitywa kwe-US $ 200 yezigidi ze-Series B yenkxaso-mali, kunye namasebe e-venture capital ye-Pfizer, i-Bayer, i-Amgen, i-Sanofi kunye nezinye iinkampani ezinkulu zamachiza ezithatha inxaxheba kutyalo-mali.I-Kernal Biologics, ekwafumene i-25 yezigidi zeedola kwi-Series A yenkxaso-mali kulo nyaka, iphinda iphuhlise i-LNPs engaqokeleli esibindini, kodwa inokuhambisa i-mRNA kwiiseli ezijoliswe kuyo ezifana nengqondo okanye izicubu ezithile.
I-Orbital Therapeutics, eyaqala kulo nyaka, iphinda ithathe ukuhanjiswa kwonyango lwe-RNA njengesikhokelo sophuhliso oluphambili.Ngokudibanisa itekhnoloji ye-RNA kunye neendlela zokuhambisa, inkampani ilindele ukwakha iqonga letekhnoloji ye-RNA ekhethekileyo enokwandisa ukuzingisa kunye nesiqingatha sobomi bonyango lwe-RNA entsha kwaye ibanike kwiindidi ezahlukeneyo zeeseli kunye nezicubu.

Uhlobo olutsha lonyango lwe-RNA luvela ngexesha lembali

Ukusukela nge-21 kaDisemba kulo nyaka, kwicandelo lonyango lwe-RNA, kuye kwakho i-31 yeziganeko zenkxaso-mali zakuqala (jonga indlela yokusebenza ekupheleni kwenqaku ukuze ufumane iinkcukacha), ezibandakanya iinkampani ze-30 zokusika (inkampani enye ifumene inkxaso-mali kabini), kunye nesixa-mali esipheleleyo se-1.74 yeebhiliyoni zeedola zaseMelika.Uhlalutyo lwezi nkampani lubonisa ukuba abatyali-mali banethemba ngakumbi malunga nezo nkampani zokusika ezilindeleke ukuba zisombulule imingeni emininzi yonyango lwe-RNA, ukuze kuqondwe ngokupheleleyo amandla onyango lwe-RNA kwaye kuxhamle izigulane ezininzi.
Kwaye kukho iinkampani ezizayo eziphuhlisa iintlobo ezintsha zonyango lwe-RNA.Ngokungafaniyo ne-oligonucleotides yendabuko, i-RNAi okanye i-mRNA, iintlobo ezintsha ze-molecule ze-RNA eziphuhliswe zezi nkampani kulindeleke ukuba ziphule ibhotile yeendlela zonyango ezikhoyo.
I-RNA yeSetyhula yenye yeendawo ezishushu kushishino.Xa kuthelekiswa ne-mRNA ene-linear, itekhnoloji ye-RNA ejikelezayo ephuhliswe yinkampani yokusika ebizwa ngokuba yi-Orna Therapeutics inokuphepha ukuqatshelwa yi-immune system kunye ne-exonucleases, enganciphisi kakhulu i-immunogenicity, kodwa inozinzo oluphezulu.Ukongezelela, xa kuthelekiswa ne-RNA yomgca, ukuhambelana okugoqiweyo kwe-RNA yesetyhula kuncinci, kwaye i-RNA yesetyhula eninzi inokulayishwa nge-LNP efanayo, iphucula ukuhanjiswa konyango lwe-RNA.Ezi mpawu zinokunceda ukuphucula amandla kunye nokuqina kwe-RNA therapeutics.
Kulo nyaka, inkampani igqibe i-US $ 221 yezigidi ze-Series B umjikelo wenkxaso-mali, kwaye yafikelela kuphando kunyeintsebenziswano yophuhliso kunye neMerck ukuya kuthi ga kwi-US$3.5 yebhiliyoni.Ukongeza, u-Orna usebenzisa i-RNA ejikelezayo ukuvelisa ngokuthe ngqo unyango lwe-CAR-T kwizilwanyana, ukugqiba ubungqinaingcamango.
Ukongeza kwisetyhula ye-RNA, itekhnoloji yokukhulisa i-mRNA (samRNAs) nayo ithandwa ngabatyali-mali.Le teknoloji isekwe kwindlela yokuzikhulisa yentsholongwane ye-RNA, enokuthi ikhuthaze ukuphindaphindwa kolandelelwano lwe-samRNA kwi-cytoplasm, yokwandisa intetho ye-kinetics ye-mRNA therapeutics, ngaloo ndlela inciphisa ukuphindaphindwa kolawulo.Xa kuthelekiswa ne-mRNA yesiko eliqhelekileyo, i-samRNA iyakwazi ukugcina amanqanaba eprotheyini afanayo malunga needosi ezingaphantsi ezili-10.Kulo nyaka, i-RNAimmune, egxile ekuphuhliseni le ntsimi, ifumene i-US $ 27 yezigidi kwi-Series A financing.
Itekhnoloji ye-tRNA nayo ifanelekile ukujongwa kuyo.Unyango olusekelwe kwi-tRNA lunokuthi "lungahoyi" i-codon yokumisa engalunganga xa iseli isenza iprotheni, ukwenzela ukuba iprotheni yobude obupheleleyo iveliswe.Kuba zininzi kakhulu iintlobo zokuyeka iicodon kunezifo ezinxulumeneyo, unyango lwe-tRNA lunamandla okuphuhlisa unyango olunye olunokunyanga izifo ezininzi.Kulo nyaka, i-hC Bioscience, egxile kunyango lwe-tRNA, inyuse i-US $ 40 yezigidi kwi-Series A yenkxaso-mali.

Ei pilogue

Njengomzekelo wonyango oluvelayo, unyango lwe-RNA luphumelele uphuhliso olukhawulezayo kwiminyaka yakutshanje, kwaye ezininzi zonyango zivunyiwe.Ukususela kuphuhliso lwamva nje kwishishini, kunokubonwa ukuba iindlela zonyango ze-RNA ezinqamlekileyo zandisa uluhlu lwezifo ezinokuthi zonyango olunjalo lukwazi ukunyanga, ukoyisa iibhotile ezahlukeneyo ekuhanjisweni okujoliswe kuzo, kunye nokuphuhlisa iamolekyu ezintsha ze-RNA ukunqoba imida yonyango ekhoyo ngokumalunga nokusebenza kunye nokuqina.imingeni emininzi.Kweli xesha litsha lonyango lwe-RNA, ezi nkampani ziphambili zinokuba yinto ekugxilwe kuyo kushishino kwiminyaka embalwa ezayo.

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