Tare da ci gaba da ci gaban fasahar ilimin halittu, alaƙar da ke tsakanin maye gurbi da lahani da cututtuka sun sami ƙarin fahimta sosai.Nucleic acid ya jawo hankali sosai saboda babban yuwuwar su na aikace-aikace a cikin ganewar asali da magance cututtuka.Magungunan Nucleic acid suna nufin DNA da aka haɗa ta wucin gadi ko gutsuttsuran RNA tare da ayyukan jiyya na cuta.Irin waɗannan magungunan na iya yin aiki kai tsaye akan ƙwayoyin cuta masu haifar da manufa ko mRNAs masu haifar da cuta, kuma suna taka rawa wajen magance cututtuka a matakin jinsin.Idan aka kwatanta da ƙananan ƙwayoyin ƙwayoyin cuta na gargajiya da magungunan ƙwayoyin cuta, magungunan nucleic acid na iya tsara maganganun kwayoyin cutar da ke haifar da cututtuka daga tushen, kuma suna da halayen "maganin bayyanar cututtuka da kuma magance tushen dalilin".Magungunan Nucleic acid suma suna da fa'ida a bayyane kamar inganci mai inganci, ƙarancin guba, da ƙayyadaddun ƙayyadaddun abubuwa.Tun lokacin da aka ƙaddamar da maganin nucleic acid fomivirsen sodium a cikin 1998, yawancin magungunan nucleic acid an yarda da su don maganin asibiti.
Magungunan nucleic acid a halin yanzu akan kasuwa a duniya galibi sun haɗa da acid nucleic acid (ASO), ƙananan RNA (siRNA), da kuma aptamers na nucleic acid.Sai dai nucleic acid aptamers (wanda zai iya wuce 30 nucleotides), magungunan nucleic acid yawanci oligonucleotides ne wanda ya ƙunshi 12 zuwa 30 nucleotides, wanda aka sani da magungunan oligonucleotide.Bugu da ƙari, miRNAs, ribozymes da deoxyribozymes sun kuma nuna babban darajar ci gaba a cikin maganin cututtuka daban-daban.Magungunan Nucleic acid sun zama ɗaya daga cikin filaye masu ban sha'awa a cikin bincike da ci gaban bioomedicine a yau.
Misalan magungunan nucleic acid da aka yarda
Antisense nucleic acid
Fasahar Antisense sabuwar fasaha ce ta haɓaka magunguna bisa ƙa'idar aikin Watson-Crick tushe, ta yin amfani da takamaiman DNA ko gutsuttsuran RNA da aka haɗa ta hanyar wucin gadi ko aka haɗa ta kwayoyin halitta don daidaita yanayin bayyanar kwayoyin halitta.Acid nucleic na antisense yana da jerin tushe wanda ya dace da RNA manufa kuma yana iya ɗaure ta musamman.Acid nucleic na antisense gabaɗaya sun haɗa da DNA antisense, RNA antisense da ribozymes.Daga cikin su, saboda halaye na babban kwanciyar hankali da ƙarancin kuɗi na DNA na antisense, DNA antisense ya mamaye matsayi mafi girma a cikin bincike na yanzu da aikace-aikacen magungunan antisense nucleic acid.
Fomivirsen sodium (sunan ciniki Vitravene) Ionis Novartis ya haɓaka.A watan Agustan 1998, FDA ta amince da shi don maganin cytomegalovirus retinitis a cikin marasa lafiya marasa lafiya (yawanci marasa lafiya AIDS), ya zama na farko da maganin nucleic acid da za a kasuwa.Fomivirsen yana hana maganganun furotin na CMV ta hanyar ɗaure takamaiman mRNA (IE2), ta haka yana daidaita maganganun ƙwayoyin cuta don cimma tasirin warkewa.Duk da haka, saboda bullar maganin rigakafin cutar kanjamau mai inganci, wanda ya rage yawan marasa lafiya, a cikin 2002 da 2006, Novartis ya soke izinin kasuwa na magungunan Fomivirsen a Turai da Amurka bi da bi, kuma an dakatar da samfurin daga kasuwa.
Mipomersen sodium (sunan ciniki Kynamro) maganin ASO ne wanda kamfanin Faransa Genzyme ya haɓaka.A cikin Janairu 2013, FDA ta amince da shi don maganin hypercholesterolemia na iyali na homozygous.Mipomersen ya hana bayyanar da furotin ApoB-100 (apolipoprotein) ta hanyar ɗaure ga ApoB-100mRNA, ta haka yana rage yawan ƙwayar cholesterol na ɗan adam, ƙananan lipoprotein mai yawa da sauran alamomi, amma saboda sakamako masu illa irin su hanta mai guba, Disamba 13, 2012, tallace-tallace na tallace-tallace a wannan rana.
A cikin Satumba 2016, Eteplirsen (sunan ciniki Exon 51) wanda Sarepta ya haɓaka don maganin Duchenne Muscular dystrophy (DMD) ya sami amincewa da FDA.Marasa lafiya na DMD ba za su iya bayyana sunadarin aikin anti-atrophic kullum ba saboda maye gurbi a cikin kwayar halittar DMD a cikin jiki.Eteplirsen musamman yana ɗaure zuwa exon 51 na pre-manzo RNA (Pre-mRNA) na furotin, yana cire exon 51, kuma ya dawo da wasu kwayoyin halitta na ƙasa.
Nusinersen magani ne na ASO wanda Spinraza ya kirkira don maganin atrophy na muscular na kashin baya kuma FDA ta amince da shi a ranar 23 ga Disamba, 2016. A cikin 2018, Inotesen ya haɓaka ta Tegsedi don kula da transthyretin amyloidosis na manya na gado ya amince da FDA.A cikin 2019, Golodirsen, wanda Sarepta ya haɓaka don maganin dystrophy na muscular Duchenne, FDA ta amince da shi.Yana da tsarin aiki iri ɗaya kamar Eteplirsen, kuma wurin aikinsa ya zama exon 53. A cikin wannan shekarar, Volanesorsen, wanda Ionisand Akcea ya haɓaka don maganin hyperchylomicronemia na iyali, ya amince da Hukumar Kula da Magunguna ta Turai (EMA).Volanesorsen yana daidaita metabolism na triglyceride ta hanyar hana samar da apolipoprotein C-Ⅲ, amma kuma yana da tasirin rage matakan platelet.
Defibrotide shine cakuda oligonucleotide tare da kaddarorin plasmin wanda Jazz ya haɓaka.Ya ƙunshi 90% DNA mai madauri guda ɗaya da kashi 10% na DNA mai madauri biyu.EMA ta amince da ita a cikin 2013 kuma daga baya FDA ta amince da ita don maganin cututtukan hanta mai tsanani.Cutar sankarau.Defibrotide na iya ƙara yawan aiki na plasmin, ƙara mai kunnawa plasminogen, inganta haɓaka tsarin thrombomodulin, da rage maganganun von Willebrand factor da masu hana plasminogen activator don cimma tasirin warkewa.
sirna
siRNA ƙaramin guntu ne na RNA tare da takamaiman tsayi da jeri da aka samar ta hanyar yanke RNA manufa.Waɗannan siRNAs na iya haifar da lalatar mRNA ta musamman da cimma tasirin yin shiru.Idan aka kwatanta da ƙananan ƙwayoyin ƙwayoyin cuta, tasirin yin shiru na kwayar halittar magungunan siRNA yana da ƙayyadaddun ƙayyadaddun abubuwa da inganci.
A ranar 11 ga Agusta, 2018, FDA ta amince da siRNA na farko magani patisiran (sunan kasuwanci Onpattro) kuma an ƙaddamar da shi a hukumance.Wannan shine ɗayan manyan cibiyoyi a cikin tarihin haɓaka fasahar kutse ta RNA.Alnylam da Genzyme, wani reshen Sanofi ne suka haɓaka Patisiran tare.Magungunan siRNA ne don maganin amyloidosis mai shiga tsakani na thyroxine.A cikin 2019, FDA ta amince da givosiran (sunan kasuwanci Givlaari) a matsayin magani na siRNA na biyu don kula da matsanancin ciwon hanta a cikin manya.A cikin 2020, Alnylam ya samar da magani na farko na nau'in I don kula da yara da manya.Lumasiran tare da babban oxaluria ya sami amincewa da FDA.A cikin Disamba 2020, Inclisiran, tare da Novartis da Alnylam suka haɓaka don maganin hypercholesterolemia babba ko gauraye dyslipidemia, EMA ta amince da su.
Aptamer
Nucleic acid aptamers su ne oligonucleotides waɗanda za su iya ɗaure ga nau'ikan kwayoyin da aka yi niyya kamar ƙananan kwayoyin halitta, DNA, RNA, polypeptides ko sunadaran da ke da alaƙa da ƙayyadaddun bayanai.Idan aka kwatanta da ƙwayoyin rigakafi, nucleic acid aptamers suna da halaye na haɗakarwa mai sauƙi, ƙananan farashi da kewayon maƙasudi, kuma suna da damar yin amfani da miyagun ƙwayoyi a cikin ganewar cututtuka, jiyya da rigakafi.
Pegaptanib shine magani na farko na nucleic acid aptamer wanda Valeant ya kirkira don maganin jiyya mai alaƙa da macular degeneration kuma FDA ta amince dashi a cikin 2004. Daga baya, EMA da PMDA sun amince dashi a cikin Janairu 2006 da Yuli 2008 kuma ya tafi kasuwa.Pegaptanib yana hana angiogenesis ta hanyar haɗuwa da tsarin sararin samaniya da haɓakar haɓakar endothelial na jijiyoyin jini don cimma tasirin warkewa.Tun daga wannan lokacin, ta ci karo da gasa daga irin magungunan Lucentis, kuma kasuwar ta ta ragu sosai.
Magungunan Nucleic acid sun zama wuri mai zafi a cikin magungunan asibiti da sabbin kasuwannin magunguna saboda tasirin warkewarsu na ban mamaki da gajeriyar yanayin ci gaba.A matsayin magani mai tasowa, yana fuskantar kalubale yayin fuskantar dama.Saboda ƙayyadaddun halayensa, ƙayyadaddun, kwanciyar hankali da ingantaccen isar da acid nucleic sun zama babban ma'auni don yin hukunci ko oligonucleotides na iya zama magungunan nucleic acid masu tasiri sosai.Abubuwan da ba a yi niyya ba koyaushe sun kasance maɓalli na magungunan nucleic acid waɗanda ba za a iya watsi da su ba.Duk da haka, kwayoyi na nucleic acid na iya rinjayar bayyanar cututtuka masu haifar da cututtuka daga tushen, kuma suna iya cimma ƙayyadaddun tsari a matakin tushe guda ɗaya, wanda ke da halaye na "maganin tushen dalilin da kuma magance alamun".Bisa la'akari da sauye-sauyen cututtuka da yawa, maganin kwayoyin halitta kawai zai iya samun sakamako na dindindin.Tare da ci gaba da haɓakawa, kamala da ci gaban fasahohin da ke da alaƙa, magungunan nucleic acid waɗanda ke wakilta ta acid nucleic na antisense, siRNA, da aptamers na nucleic acid tabbas za su tayar da wani sabon tashin hankali a cikin maganin cututtuka da masana'antar harhada magunguna.
Rabubuwan da ke faruwa:
[1] Liu Shaojin, Feng Xuejiao, Wang Junshu, Xiao Zhengqiang, Cheng Pingsheng.Binciken kasuwa na magungunan nucleic acid a cikin ƙasata da matakan kariya[J].Jaridar Sinanci na Injiniyan Halittu, 2021, 41 (07): 99-109.
[2] Chen Wenfei, Wu Fuhua, Zhang Zhirong, Sun Xun.Ci gaban bincike a cikin ilimin harhada magunguna na kasuwannin magungunan nucleic acid[J].Jaridar Sinanci na Magunguna, 2020, 51 (12): 1487-1496.
[3] Wang Jun, Wang Lan, Lu Jiazhen, Huang Zhen.Binciken inganci da ci gaban bincike na magungunan nucleic acid [J].Jaridar Sinawa ta Sabbin Magunguna, 2019, 28 (18): 2217-2224.
Game da marubucin: Sha Luo, ma'aikaciyar bincike da raya magunguna ta kasar Sin, a halin yanzu tana aiki da wani babban kamfanin bincike da raya magunguna na cikin gida, kuma ta himmatu wajen yin bincike da bunkasa sabbin magungunan kasar Sin.
Samfura masu alaƙa:
Lokacin aikawa: Nuwamba-19-2021
