Xigasho: WuXi AppTec

Sanadihii la soo dhaafay, goobta daawaynta RNA waxay muujisay isbeddel qarxa-5tii sano ee la soo dhaafay oo keliya, 11 daawaynta RNA waxaa ansixisay FDA, tiradan xitaa way ka badan tahay wadarta daawaynta RNA ee hore loo ansixiyay!Marka la barbardhigo daawaynta dhaqameed, daawaynta RNA waxay si dhakhso ah u horumarin kartaa daawaynta la beegsanayo oo leh heerar sare oo guul leh ilaa iyo inta taxanaha hiddasidaha bartilmaameedka la og yahay.Dhanka kale, inta badan daawaynta RNA ayaa wali diyaar u ah oo kaliya in lagu daweeyo cudurada naadirka ah, iyo horumarinta daawaynta noocan oo kale ah ayaa wali la kulma caqabado badan oo ku saabsan adkeysiga daawaynta, badbaadada, iyo bixinta.Maqaalka maanta, thekooxda nuxurka ee WuXi AppTec waxay dib u eegis ku samayn doontaa horumarka dhinaca daawaynta RNA sanadkii la soo dhaafay, waxaanay akhristayaasha la sugi doonaan mustaqbalka goobtan soo ifbaxday.

v 11 daawaynta RNA ama tallaalada ayaa ay ansixisay FDA 5tii sano ee la soo dhaafay

Laga soo bilaabo cudurrada dhifka ah ilaa cudurrada caadiga ah, ubaxyo badan ayaa ubaxa

Cudurka faafa ee taajka cusub, tallaalka mRNA wuxuu ka dhashay meel aan jirin wuxuuna ka helay feejignaan ballaaran warshadaha.Kadib markiiHorumarka laga gaaray horumarinta tallaallada cudurrada faafa, caqabad kale oo weyn oo soo food saartay tignoolajiyada mRNA waa in la ballaariyo baaxadda codsiga daaweynta iyo ka hortagga cudurro badan.
Iyaga ka mid ah,Tallaalka kansarka ee gaarka ah waa goob muhiim ah oo laga codsado tignoolajiyada mRNAWaxaan sidoo kale aragnay natiijooyin caafimaad oo wanaagsan oo dhowr tallaal oo kansar ah sanadkan.Bishan oo keliya, tallaalka kansarka gaarka ah ee ay si wadajir ah u sameeyeen Moderna iyo Merck, oo ay weheliso PD-1 inhibitor Keytruda,hoos u dhigtay khatartasoo noqoshada ama dhimashada bukaanada leh marxaladda III iyo IV melanoma ka dib markii dhammaystiran oo burada dib-u-soo-celinta 44% (marka la barbardhigo monotherapy Keytruda).War saxaafadeedka ayaa tilmaamay in tani ay tahay markii ugu horeysay ee tallaalka kansarka mRNA uu muujiyo waxtarka daaweynta melanoma ee tijaabo caafimaad oo kala duwan, taas oo ah dhacdo calaamad u ah horumarinta tallaalada kansarka mRNA.
Intaa waxaa dheer, tallaalada mRNA waxay sidoo kale kor u qaadi karaan saameynta daaweynta ee daaweynta unugyada.Tusaale ahaan, daraasad ay samaysay BioNTech ayaa tilmaantay in haddii bukaannada marka hore lagu shubo qiyaas yar oo ah daawaynta CAR-T ee CLDN6.BNT211, ka dibna lagu duro tallaalka mRNA ee codeeynaya CLDN6, waxay kicin karaan unugyada CAR-T ee vivo iyagoo muujinaya CLDN6 oogada unugyada antigen-soo bandhigaya.Kordhinta, taas oo kor u qaadaysa saamaynta ka hortagga kansarka.Natiijooyinka hordhaca ah waxay muujiyeen in 4 ka mid ah 5 bukaan ee helay daawaynta isku dhafka ah ay heleen jawaab qayb ahaan, ama 80%.

Marka lagu daro daawaynta mRNA, daawaynta oligonucleotide iyo daawaynta RNAi waxay sidoo kale ku guulaysteen natiijooyin wanaagsan balaarinta baaxada cudurada.Daawaynta cagaarshow B raaga, ku dhawaad ​​30% bukaanada ma ogaan karaan cagaarshowga B oogada antigen iyo fayraska cagaarshow B DNA in vivo ka dib markii la isticmaalo daawaynta oligonucleotide antisensebepirovirsen oo ay si wadajir ah u soo saareen GSK iyo Ionismuddo 24 toddobaad ah.Bukaannada qaarkood, xitaa 24 toddobaad ka dib joojinta daawaynta, calaamadahan cagaarshowga B weli lagama ogaan jidhka.
Nasiib darro, daaweynta RNAiVIR-2218 oo ay si wadajir ah u sameeyeen Vir Biotechnology iyo Alnylam ayaa la isku darayoo leh interferon α, iyo marxaladda 2 ee tijaabooyinka kiliinikada, qiyaastii 30% bukaannada cagaarshow B ee daba-dheeraada ayaa sidoo kale ku guuldareystay inay ogaadaan cagaarshowga B dusha antigen (HBsAg).Intaa waxaa dheer, bukaannadani waxay soo saareen unugyada difaaca jirka ee ka hortagga borotiinka cagaarshow B, taas oo muujinaysa jawaab-celin wanaagsan oo habdhiska difaaca ah.Isku soo wada duuboo natiijooyinkan, warshaduhu waxay tilmaamayaan in daawaynta RNA ay noqon karto furaha daawaynta shaqaynaysa ee cagaarshowga B.
Tani waxay noqon kartaa uun bilowga daawaynta RNA ee cudurada caadiga ah.Sida laga soo xigtay dhuumaha R&D ee Alnylam, waxay sidoo kale horumarinaysaa daawaynta RNAi ee daaweynta hypertension, cudurka Alzheimers, iyo steatohepatitis-ka aan khamriga ahayn, mustaqbalkana waa mid mudan in la sugo.

Jebinta cirifka dhalooyinka ee bixinta daawaynta RNA

Bixinta daaweynta RNA waa mid ka mid ah caqabadaha xaddidaya codsigeeda.Saynis yahanadu waxay sidoo kale horumarinayaan teknoolojiyad kala duwan si ay si gaar ah ugu gudbiyaan daawaynta RNA xubnaha iyo unugyada aan ahayn beerka.
Mid ka mid ah hababka suurtagalka ah ayaa ah in "lagu xiro" RNA-yada daweynta leh unugyo gaar ah oo unug gaar ah.Tusaale ahaan, Avidity Biosciences ayaa dhawaan ku dhawaaqday in aaladeeda tignoolajiyada ay ku dari karto unugyada difaaca jirka ee oligonucleotidessi wax ku ool ah u xidh siRNA-yada.loo diro muruqa lafaha.War-saxaafadeedka ayaa tilmaamay in tani ay tahay markii ugu horreysay ee siRNA si guul leh loo bartilmaameedsado loona gaarsiiyo unugyada muruqa bini'aadamka, taas oo ah horumar weyn oo laga sameeyay dhinaca daaweynta RNA.

Isha sawirka: 123RF

Marka lagu daro tignoolajiyada isku xidhka antibody-ga, tiro shirkado ah oo soo saaraya nanoparticles lipid nanoparticles (LNP) ayaa sidoo kale "kor u qaadaya" sidayaal noocaas ah.Tusaale ahaan, Dib u codee Therapeuticwaxay isticmaashaa xubinteeda gaarka ah ee Bartilmaameedka LNP Technology (SORT) si ay u gaarsiiso noocyo kala duwan oo daawaynta RNA ah sambabada, beeryarada, beerka iyo xubnaha kale.Sannadkan, shirkaddu waxay ku dhawaaqday inay dhamaystirtay US$ 200 milyan oo doolar oo wareeg ah oo maalgelin ah, iyada oo waaxaha raasumaalka ee Pfizer, Bayer, Amgen, Sanofi iyo shirkado kale oo dawooyin ah ay ka qayb qaadanayaan maalgashiga.Kernal Biologics , oo sidoo kale heshay $ 25 million ee maalgelinta Taxanaha A sanadkan, ayaa sidoo kale horumarinaysa LNP-yada aan ku ururin beerka, laakiin waxay gaarsiin karaan mRNA si ay u beegsadaan unugyada sida maskaxda ama burooyinka gaarka ah.
Daaweynta Orbital Therapeutics , oo laga dooday sanadkan, ayaa sidoo kale qaadata bixinta daaweynta RNA sida jihada horumarinta muhiimka ah.Marka la isku daro tignoolajiyada RNA iyo hababka gaarsiinta, shirkaddu waxay rajaynaysaa inay dhisto madal tignoolajiyada RNA gaar ah kaas oo kordhin kara adkaysiga iyo nolosha nuska ah ee daaweynta RNA ee hal-abuurka leh oo u gudbisa noocyo kala duwan oo unugyo iyo unugyo kala duwan ah.

Nooc cusub oo daawaynta RNA ah ayaa soo baxaysa wakhtiga taariikhiga ah

Laga bilaabo Diisambar 21 ee sanadkan, dhinaca daawaynta RNA, waxaa jiray 31 dhacdooyin maalgelineed oo heer hore ah (fiiri habka dhamaadka maqaalka si aad u hesho faahfaahin), oo ku lug leh 30 shirkadood oo heersare ah (hal shirkad ayaa laba jeer maalgelin heshay), iyada oo wadarta guud ee maalgelinta ay tahay 1.74 bilyan oo doolarka Mareykanka ah.Falanqaynta shirkadahan waxay muujineysaa in maalgashadayaasha ay aad ugu rajo weyn yihiin shirkadahaas go'ay ee laga filayo inay xalliyaan caqabado badan oo daawaynta RNA ah, si ay si buuxda u garawsadaan awoodda daawaynta RNA oo ay uga faa'iidaystaan ​​bukaanno badan.
Oo waxaa jira shirkado soo socda oo soo saaraya noocyo cusub oo ah daweynta RNA.Si ka duwan oligonucleotides-dhaqameedka, RNAi ama mRNA, noocyada cusub ee molecules RNA ee ay sameeyeen shirkadahan ayaa la filayaa inay ka gudbaan ciribtirka daweynta jira.
Wareegtada RNA waa mid ka mid ah meelaha kulul ee warshadaha.Marka la barbar dhigo mRNA toosan, tignoolajiyada wareegtada RNA ee ay soo saartay shirkad heersare ah oo lagu magacaabo Orna Therapeutics waxay ka fogaan kartaa in lagu aqoonsado habka difaaca jirka iyo exonucleases, taas oo aan kaliya si weyn u dhimin difaaca jirka, laakiin sidoo kale leh xasilooni sare.Intaa waxaa dheer, marka la barbar dhigo RNA toosan, isku-duubnaanta isku laabma ee RNA wareegtadu waa ka yar tahay, iyo RNA wareegyo badan ayaa lagu rari karaa isla LNP, hagaajinta waxtarka bixinta daaweynta RNA.Astaamahan ayaa kaa caawin kara hagaajinta awoodda iyo adkeysiga daaweynta RNA.
Sannadkan, shirkaddu waxay dhamaystirtay US$ 221 milyan wareeg maaliyadeed oo taxane B ah, waxayna sidoo kale gaartay cilmi-baaris iyoiskaashiga horumarinta ee Merck ilaa US$3.5 bilyan.Intaa waxaa dheer, Orna waxay sidoo kale isticmaashaa RNA wareeg ah si ay si toos ah ugu dhaliso daaweynta CAR-T ee xayawaanka, buuxinta caddayntafikradda.
Marka lagu daro RNA wareeg ah, tignoolajiyada is-weynaynta mRNA (samRNAs) ayaa sidoo kale ay door bideen maalgashadayaasha.Farsamadani waxay ku salaysan tahay habka is-kordhinta ee fayraska RNA, taas oo keeni karta ku-noqoshada taxanaha samRNA ee cytoplasm, sii dheeraysa muujinta kinetics ee daaweynta mRNA, taas oo yareynaysa inta jeer ee maamulka.Marka la barbardhigo mRNA-ka tooska ah ee dhaqameed, samRNA waxa ay awoodaa in ay ilaaliso heerarka muujinta borotiinka ee la midka ah qiyaastii 10-laab qiyaasood oo hoose.Sannadkan, RNAimmune, oo diiradda saareysa horumarinta goobtan, waxay heshay US $ 27 milyan maalgelinta Taxanaha A.
Tignoolajiyada tRNA waxay sidoo kale mudan tahay in la sugo.Daawaynta ku salaysan tRNA waxay "iska indho tiraysaa" koodka joogsiga qaldan marka unugu sameeyo borotiinka, si borotiinka dhererka buuxa ee caadiga ah loo soo saaro.Sababtoo ah waxaa jira noocyo aad u yar oo ah codons-ka joogsiga marka loo eego cudurrada la xiriira, terabiyada tRNA waxay awood u leedahay inay horumariso hal daawayn oo daweyn kara cudurro badan.Sannadkan, hC Bioscience, oo diiradda saaraya daawaynta tRNA, ayaa kor u qaaday wadarta US $ 40 milyan ee maalgelinta Taxanaha A.

Eduuliye

Qaabka daawaynta ee soo ifbaxday, daawaynta RNA waxa ay gaadhay horumar degdeg ah sanadihii ugu dambeeyay, daawayno badana waa la ansixiyay.Laga soo bilaabo horumarkii ugu dambeeyay ee warshadaha, waxaa la arki karaa in daweynta RNA-ga gooyay ay ballaarineyso noocyada cudurrada ay daawaynta noocan oo kale ah daweyn karaan, ka gudbaan caqabadaha kala duwan ee gaarsiinta la beegsanayo, iyo horumarinta unugyada cusub ee RNA si ay uga gudbaan xaddidaadda daaweynta hadda jirta marka loo eego waxtarka iyo cimri dhererka.caqabado badan.Xilligan cusub ee daawaynta RNA, shirkadahan wax-soo-saarka leh ayaa laga yaabaa inay noqdaan kuwa diiradda saaraya warshadaha dhowrka sano ee soo socda.

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