Horumarka joogtada ah ee tignoolajiyada bayoolajiga molecular, xidhiidhka ka dhexeeya isbeddellada hidda-wadaha iyo cilladaha iyo cudurrada ayaa helay faham qoto dheer oo dheeraad ah.Asiidhyada nukliyeerka ayaa soo jiitay dareen badan sababtoo ah awooddooda weyn ee codsiga ee ogaanshaha iyo daaweynta cudurrada.Daawooyinka aashitada nukliyeerka waxay tixraacaan DNA si macmal ah loo sameeyay ama jajabyada RNA ee leh hawlaha daaweynta cudurka.Daawooyinka noocan oo kale ah waxay si toos ah ugu dhaqmi karaan hidde-sideyaasha bartilmaameedka ah ee cudur-sida ama cudurka- keena bartilmaameedka mRNA-yada, waxayna door ka ciyaaraan daaweynta cudurrada heerka hidda-wadaha.Marka la barbar dhigo dawooyinka molecule yar yar ee dhaqameed iyo dawooyinka lidka ku ah jidhka, dawooyinka nucleic acid waxay nidaamin karaan muujinta hidde-sideyaasha cudur-sidaha ee xididka, waxayna leeyihiin astaamaha "daaweynta calaamadaha iyo daaweynta sababta asaasiga ah".Daawooyinka aashitada nukliyeerka sidoo kale waxay leeyihiin faa'iidooyin muuqda sida waxtarka sare, sunta hoose, iyo gaarnimada sare.Tan iyo markii ugu horeysay ee daawada nucleic acid fomivirsen sodium la bilaabay 1998, daawooyin badan oo nucleic acid ah ayaa loo oggolaaday daaweynta kiliinikada.

Daawooyinka aashitada nucleic-ka ah ee hadda suuqa ka jira inta badan waxaa ka mid ah antisense nucleic acid (ASO), RNA faragelin yar (siRNA), iyo aptamers nucleic acid.Marka laga reebo nukleic acid aptamers (kaas oo laga yaabo in ay dhaafaan 30 nucleotide), daawooyinka nucleic acid inta badan waa oligonucleotides oo ka kooban 12 ilaa 30 nucleotide, oo sidoo kale loo yaqaan daawooyinka oligonucleotide.Intaa waxaa dheer, miRNA-yada, ribozymes iyo deoxyribozymes ayaa sidoo kale muujiyay qiimaha horumarka weyn ee daaweynta cudurrada kala duwan.Daawooyinka Nucleic acid waxay noqdeen mid ka mid ah meelaha ugu rajo weyn ee cilmi baarista iyo horumarinta biomedicine maanta.

Tusaalooyinka daawooyinka nucleic acid ee la ansixiyay

Antisense nucleic acid

Tignoolajiyada Antisense-ku waa tignoolajiyada horumarinta dawooyinka cusub ee ku salaysan mabda'a dhammaystirka saldhigga Watson-Crick, iyadoo la adeegsanayo DNA-ga dhammaystirka gaar ah ama jajabyada RNA oo si macmal ah u farsameeyay ama u farsameeyay noolaha si si gaar ah loogu habeeyo muujinta hiddo-wadaha bartilmaameedka ah.Aashitada nucleic-ka lidka ku ah waxay leedahay taxane sal ah oo kaabaya bartilmaameedka RNA oo si gaar ah ugu xidhi kara.Asiidhyada nucleic-ka-hortagga ah guud ahaan waxaa ka mid ah DNA-da-dareenka, RNA-da-dareenka iyo ribozymes.Waxaa ka mid ah, astaamaha xasilloonida sare iyo qiimaha hooseeya ee DNA-da lidka-diidka awgeed, DNA-da lidka ku ah waxay ku jirtaa booska ugu sarreeya cilmi-baarista hadda iyo adeegsiga dawooyinka nucleic acid-ka lidka ku ah.

Fomivirsen sodium (magaca ganacsiga Vitravene) waxaa sameeyay Ionis Novartis.Bishii Agoosto 1998, FDA waxay u ogolaatay daawaynta cytomegalovirus retinitis ee bukaannada difaaca jirka (gaar ahaan bukaannada AIDS-ka), oo noqday daawadii ugu horreysay ee nucleic acid ee la suuq geeyo.Fomivirsen waxay joojisaa muujinta borotiinka qayb ka mid ah CMV iyada oo ku xidhan mRNA gaar ah (IE2), taas oo nidaaminaysa muujinta hiddo-wadaha fayraska si loo gaaro saamaynta daaweynta.Si kastaba ha ahaatee, iyada oo ay ugu wacan tahay soo ifbaxa daaweynta waxtarka leh ee waxtarka leh ee antiretroviral, taas oo si weyn u yaraysay tirada bukaannada, 2002 iyo 2006, Novartis waxay baabi'isay oggolaanshaha suuqa ee daawooyinka Fomivirsen ee Yurub iyo Maraykanka siday u kala horreeyaan, badeecaduna waa laga joojiyay suuqa.

Mipomersen sodium (magaca ganacsiga Kynamro) waa daawo ASO ah oo ay samaysay shirkadda Faransiiska ee Genzyme.Bishii Janaayo 2013, FDA waxay u ogolaatay daawaynta hypercholesterolemia qoyska homozygous.Mipomersen waxay xakameysaa muujinta borotiinka ApoB-100 (apolipoprotein) iyada oo ku xidhan ApoB-100mRNA, taas oo si weyn u yaraynaysa kolestaroolka lipoprotein-yar ee cufnaanta bini'aadamka, lipoprotein cufnaanta hoose iyo tilmaamayaasha kale, laakiin ay sabab u tahay waxyeellooyin sida sunta beerka, December 13, 2012 iibka daroogada ee isla maalintaas.

Bishii Sebtembar 2016, Eteplirsen (magaca ganacsiga Exon 51) oo ay samaysay Sarepta ee daawaynta Duchenne muscular dystrophy (DMD) waxaa ansixiyay FDA.Bukaannada DMD caadi ahaan ma sheegi karaan borotiinka ka hortagga atrophic ee shaqeynaya sababtoo ah isbeddellada ku jira hidda-wadaha DMD ee jirka.Eteplirsen waxay si gaar ah ugu xidhan tahay exon 51 oo ka mid ah rasuulkii hore ee RNA (Pre-mRNA) ee borotiinka, waxay ka saartaa exon 51, waxayna dib u soo celisaa qaar ka mid ah hiddo-wadaha hoose ee muujinta caadiga ah ee, qorista iyo tarjumaada si loo helo qayb ka mid ah dystrophin, si loo gaaro saameynta daaweynta.

Nusinersen waa daawo ASO ah oo ay soo saartay Spinraza si loogu daweeyo atrophy muruqa laf-dhabarka waxaana ansixiyay FDA December 23, 2016. 2018, Inotesen oo ay samaysay Tegsedi si loogu daaweeyo transthyretin amyloidosis ee dadka waaweyn ee dhaxalka ah waxaa ansixiyay FDA.Sannadka 2019, Golodirsen, oo ay soo saartay Sarepta oo loogu talagalay daawaynta dystrophy muruqa Duchenne, waxaa ansixiyay FDA.Waxay leedahay hab la mid ah sida Eteplirsen, iyo goobta ay ka hawlgala waxay noqotaa exon 53. Isla sanadkaas, Volanesorsen, oo ay si wadajir ah u sameeyeen Ionisand Akcea ee daaweynta hyperchylomicronemia qoyska, waxaa ansixiyay Wakaaladda Daawooyinka Yurub (EMA).Volanesorsen waxa ay xakameysaa dheef-shiid kiimikaadka triglyceride isaga oo ka hortagaya soo saarista apolipoprotein C-Ⅲ, laakiin waxa kale oo ay leedahay saamaynta dhinaca hoos u dhigista heerarka platelet.

Defibrotide waa isku dhafka oligonucleotide oo leh waxyaabo plasmin ah oo uu sameeyay Jazz.Waxay ka kooban tahay 90% DNA-da hal-xadhigleed DNA iyo 10% DNA laba-xadhigleed.Waxaa ansixiyay EMA sanadkii 2013 ka dibna waxaa u ansixisay FDA daawaynta xididdada beerka ee daran.Cudurka qarsoon.Defibrotide waxay kordhin kartaa waxqabadka plasmin, kordhinta firfircoonida plasminogen, kor u qaadida nidaaminta thrombomodulin, waxayna yaraynaysaa muujinta von Willebrand factor iyo plasminogen activator inhibitors si loo gaaro saamaynta daweynta

siRNA     

siRNA waa qayb yar oo RNA ah oo leh dherer gaar ah iyo isku xigxig oo la soo saaray iyada oo la jarayo RNA bartilmaameedka.SiRNA-yadani waxay si gaar ah u kicin karaan hoos u dhaca mRNA-ga bartilmaameedka ah waxayna gaaraan saamaynta aamusinta hidda-wadaha.Marka la barbar dhigo dawooyinka unugyaraha yar yar ee kiimikaad, saamaynta aamusinta hidda-wadaha ee dawooyinka siRNA waxa ay leedahay gaar gaar ah iyo hufnaan sare.

Agoosto 11, 2018, siRNA dawadii ugu horeysay patisiran (magaca ganacsiga Onpattro) waxaa ansixiyay FDA oo si rasmi ah loo bilaabay.Tani waa mid ka mid ah dhacdooyinka ugu waaweyn ee taariikhda horumarinta tignoolajiyada faragelinta RNA.Patisiran waxaa si wada jir ah u soo saaray Alnylam iyo Genzyme, oo ah shirkad hoos timaada Sanofi.Waa daawada siRNA ee daawaynta amyloidosis dhexdhexaadinta thyroxine.2019, givosiran (magaca ganacsiga Givlaari) waxaa ansixisay FDA inay tahay dawada labaad ee siRNA ee daawaynta beerka beerka ee dadka waaweyn.Sanadka 2020, Alnylam waxa ay soo saartay dawada nooceeda koowaad ee daaweynta carruurta iyo dadka waaweyn.Lumasiran oo leh oxaluria sare waxaa ansixiyay FDA.Bishii Disembar 2020, Inclisiran, oo ay si wadajir ah u soo saareen Novartis iyo Alnylam oo loogu talagalay daawaynta hypercholesterolemia dadka waaweyn ama dyslipidemia isku dhafan, ayaa waxaa oggolaatay EMA.

Abtamer

Nucleic acid aptamers waa oligonucleotides kuwaas oo ku xidhi kara noocyo kala duwan oo unugyo bartilmaameed ah sida molecules organic yaryar, DNA, RNA, polypeptides ama borotiinno leh xiriir sare iyo gaar ahaaneed.Marka la barbardhigo unugyada difaaca jirka, nucleic acid aptamers waxay leeyihiin sifooyin isku dhafan oo fudud, qiimo jaban iyo bartilmaameedyo ballaaran, waxayna leeyihiin awood ballaaran oo loogu talagalay codsiga daroogada ee ogaanshaha cudurka, daaweynta iyo ka hortagga.

Pegaptanib waa daawadii ugu horeysay ee nucleic acid aptamer oo ay samaysay Valeant si loogu daweeyo da'da qoyan ee la xiriirta macular degeneration waxaana ansixiyay FDA 2004. Kadib, waxaa ansixiyay EMA iyo PMDA bishii Janaayo 2006 iyo Luulyo 2008 waxayna tagtay suuqa.Pegaptanib wuxuu joojiyaa angiogenesis-ka iyada oo loo marayo isku-dhafka qaab-dhismeedka bannaanka iyo korriinka korriinka xididdada dhiigga si loo gaaro saameynaha daweynta.Tan iyo markaas, waxay la kulantay tartan dawooyinka la midka ah ee Lucentis, iyo saamigeeda suuqa ayaa aad hoos ugu dhacay.

Daawooyinka aashitada nukliyeerka waxay noqdeen meel kulul ee daawada kiliinikada iyo suuqa cusub ee dawooyinka sababtoo ah saameyntooda daaweyneed ee cajiibka ah iyo wareegga korriinka gaaban.Maandooriye soo baxaya, waxa ay la kulantaa caqabado marka ay la kulanto fursadaha.Sababo la xiriira sifooyinka dibadda, gaar ahaan, xasiloonida iyo bixinta wax ku ool ah ee acids nucleic ayaa noqday shuruudaha ugu muhiimsan ee lagu xukumay in oligonucleotides noqon karaan daawooyinka nucleic acid aad waxtar u leh.Saamaynta ka baxsan bartilmaameedka ayaa had iyo jeer ahaa barta muhiimka ah ee daawooyinka nucleic acid ee aan la iska indho tiri karin.Si kastaba ha noqotee, dawooyinka nucleic acid waxay saameyn karaan muujinta hidde-sideyaasha cudur-sidaha ee xididka, waxayna ku gaari karaan isku xigxiga gaarka ah ee heerka hal-saldhigga, kaas oo leh sifooyinka "daaweynta sababta asaasiga ah iyo daaweynta calaamadaha".Marka la eego kala duwanaanshaha cudurro badan oo badan, kaliya daaweynta hidde-socodka ayaa gaari karta natiijooyin joogto ah.Horumarka joogtada ah, kaamilnimada iyo horumarka tignoolajiyada la xidhiidha, daawooyinka nucleic acid oo ay matalaan asiidhyada nucleic-ka antisense, siRNA, iyo aptamers nucleic acid ayaa hubaal ah inay dejin doonaan mowjad cusub oo ku saabsan daaweynta cudurka iyo warshadaha dawooyinka.

Rdareenka:

[1] Liu Shaojin, Feng Xuejiao, Wang Junshu, Xiao Zhengqiang, Cheng Pingsheng.Falanqaynta suuqa ee dawooyinka aashitada nukliyeerka ah ee dalkayga iyo ka-hortagga[J].Joornaalka Shiinaha ee Injineerinka Nafleyda, 2021, 41 (07): 99-109.

[2] Chen Wenfei, Wu Fuhua, Zhang Zhirong, Sun Xun.Horumarka cilmi baarista ee farmashiyaha ee dawooyinka aashitada nucleic-ka ah ee la suuq geeyey[J].Joornaalka Shiinaha ee Daawooyinka, 2020, 51(12): 1487-1496.

[3] Wang Jun, Wang Lan, Lu Jiazhen, Huang Zhen.Falanqaynta waxtarka iyo horumarka cilmi-baarista ee dawooyinka aashitada nukliyeerka ah ee la suuq geeyey[J].Joornaalka Shiinaha ee Dawooyinka Cusub, 2019, 28 (18): 2217-2224.

Ku saabsan qoraaga: Sha Luo, oo ah cilmi-baare cilmi-baaris iyo shaqaale horumarineed oo Shiinaha ah, waxay hadda u shaqeysaa shirkad weyn oo cilmi-baarista iyo horumarinta daroogada gudaha, waxayna u heellan tahay cilmi-baarista iyo horumarinta daawooyinka cusub ee Shiinaha.

Alaabta la xidhiidha:

Qalabka tooska ah ee gacanta ee RT-qPCR