Nekuenderera mberi kwekuvandudzwa kwema molecular biology tekinoroji, hukama pakati pekuchinja kwemajini uye hurema nezvirwere hwakawedzera kunzwisisa kwakadzama.Nucleic acids yakwezva kutarisisa zvakanyanya nekuda kwekugona kwavo kukuru kwekushandisa mukuongororwa uye kurapwa kwezvirwere.Nucleic acid mishonga inoreva zvakagadzirirwa DNA kana RNA zvimedu zvine mabasa ekurapa chirwere.Mishonga yakadai inogona kuita zvakanangana nechirwere-chinokonzera chinangwa chemajini kana chirwere chinokonzera chinangwa mRNAs, uye kuita basa mukurapa zvirwere padanho remajini.Kuenzaniswa nemishonga yemamorekuru madiki echinyakare uye mishonga yekurwisa antibody, nucleic acid mishonga inogona kudzora mataurirwo emajini anokonzera chirwere kubva pamudzi, uye ane hunhu hwe "kurapa zviratidzo uye kurapa chinokonzera".Nucleic acid zvinodhaka zvakare zvine mabhenefiti ari pachena akadai sekunyanya kushanda zvakanaka, kuderera muchetura, uye hunyanzvi hwepamusoro.Kubva yekutanga nucleic acid drug fomivirsen sodium yakatangwa muna 1998, mishonga yakawanda ye nucleic acid yakatenderwa kurapwa.

Iyo nucleic acid mishonga parizvino iri pamusika wepasi rose inonyanya kusanganisira antisense nucleic acid (ASO), diki inopindira RNA (siRNA), uye nucleic acid aptamers.Kunze kweiyo nucleic acid aptamers (iyo inogona kudarika 30 nucleotides), nucleic acid mishonga inowanzova oligonucleotides inoumbwa ne12 kusvika ku30 nucleotides, inozivikanwawo se oligonucleotide zvinodhaka.Mukuwedzera, miRNAs, ribozymes uye deoxyribozymes zvakaratidzawo kukosha kukuru kwekusimudzira mukurapa zvirwere zvakasiyana-siyana.Nucleic acid mishonga yave imwe yeminda inovimbisa mukutsvaga nekusimudzira biomedicine nhasi.

Mienzaniso yemishonga inobvumirwa nucleic acid

Antisense nucleic acid

Tekinoroji yeAntisense tekinoroji nyowani yekuvandudza zvinodhaka yakavakirwa pamusimboti weWatson-Crick base complementation, ichishandisa yakanangana neDNA kana RNA zvimedu zvakagadziridzwa kana kugadzirwa nechipenyu kuti zvinyatso gadzirisa kutaura kwemajini anonangwa.Iyo antisense nucleic acid ine base sequence inopindirana kune yakananga RNA uye inogona kunyatso sunga kwairi.Antisense nucleic acids kazhinji inosanganisira antisense DNA, antisense RNA uye ribozymes.Pakati pavo, nekuda kwehunhu hwekugadzikana kwepamusoro uye mutengo wakaderera weantisense DNA, antisense DNA inotora chinzvimbo chikuru mukutsvagisa kwazvino uye kushandiswa kweantisense nucleic acid zvinodhaka.

Fomivirsen sodium (zita rekutengesa Vitravene) yakagadzirwa naIonis Novartis.Muna Nyamavhuvhu 1998, iyo FDA yakaibvumidza kuti irapwe cytomegalovirus retinitis muvarwere vasina immunocompromised (kunyanya varwere veAIDS), ikava yekutanga nucleic acid mushonga kutengeswa.Fomivirsen inhibits partial protein expression of CMV nekusunga kune chaiyo mRNA (IE2), nokudaro ichironga kutaura kwemajini evhairasi kuti iwane kurapa.Zvakadaro, nekuda kwekubuda kwemushonga wema antiretroviral therapy, izvo zvakaderedza huwandu hwevarwere, muna 2002 na2006, Novartis akadzima mvumo yemusika yemishonga yeFomivirsen kuEurope nekuUnited States zvichiteerana, uye chigadzirwa chakamiswa pamusika.

Mipomersen sodium (zita rekutengeserana Kynamro) mushonga weASO wakagadzirwa nekambani yeFrance Genzyme.Muna Ndira 2013, iyo FDA yakaibvumidza kurapwa kwehomozygous mhuri hypercholesterolemia.Mipomersen inhibisa kutaura kweApoB-100 protein (apolipoprotein) nekusunga kuApoB-100mRNA, nekudaro ichideredza zvakanyanya vanhu low-density lipoprotein cholesterol, low-density lipoprotein nezvimwe zviratidzo, asi nekuda kwemhedzisiro yakadai sechepfu yechiropa, Zvita 13, 2012 yakarambwawo rezinesi rekutengesa zvinodhaka Pazuva rimwe chete reEMA.

MunaGunyana 2016, Eteplirsen (zita rekutengesa Exon 51) rakagadzirwa neSarepta pakurapa Duchenne muscular dystrophy (DMD) yakabvumidzwa neFDA.Varwere veDMD havagone kuratidza mashandiro e-anti-atrophic protein nekuda kwekuchinja kweiyo DMD gene mumuviri.Eteplirsen inosungirira zvakananga ku exon 51 yepre-messenger RNA (Pre-mRNA) yeprotein, inobvisa exon 51, uye inodzoreredza mamwe majene ezasi Matauriro akajairika e, kunyora uye kududzira kuti awane chikamu chedystrophin, kuitira kuti uwane mhedzisiro yekurapa.

Nusinersen mushonga weASO wakagadzirwa naSpinraza kuitira kurapwa kwespinal muscular atrophy uye yakagamuchirwa neFDA musi waDecember 23, 2016. Muna 2018, Inotesen yakagadzirwa naTegsedi kuitira kurapwa kwevanhu vakuru venhaka transthyretin amyloidosis yakagamuchirwa neFDA.Muna 2019, Golodirsen, yakagadziridzwa neSarepta yekurapa Duchenne muscular dystrophy, yakabvumidzwa neFDA.Iine nzira imwechete yekuita seEteplirsen, uye nzvimbo yayo yekuita inova exon 53. Mugore rimwe chete, Volanesorsen, yakabatanidzwa neIonisand Akcea yekurapa kwemhuri hyperchylomicronemia, yakagamuchirwa neEuropean Medicines Agency (EMA).Volanesorsen inodzora triglyceride metabolism nekudzivisa kugadzirwa kweapolipoprotein C-Ⅲ, asi inewo mhedzisiro yekudzikisa mazinga eplatelet.

Defibrotide musanganiswa we oligonucleotide une plasmin zvivakwa zvakagadzirwa neJazz.Iine 90% DNA imwe-stranded DNA uye 10% DNA yakapetwa kaviri.Yakatenderwa neEMA muna 2013 uye yakazobvumidzwa neFDA kurapwa kweakanyanya hepatic tsinga.Occlusive chirwere.Defibrotide inogona kuwedzera basa re plasmin, kuwedzera plasminogen activator, kukurudzira kumusoro-mutemo we thrombomodulin, uye kuderedza kutaura kwe von Willebrand factor uye plasminogen activator inhibitors kuti uwane kurapa mhedzisiro.

siRNA     

siRNA chidimbu chidiki cheRNA chine hurefu chaihwo uye kutevedzana kunogadzirwa nekucheka chinangwa RNA.Aya ma siRNA anogona kunyanya kukonzeresa kuderedzwa kwechinangwa mRNA uye kuwana gene kunyaradza mhedzisiro.Kuenzaniswa nemakemikari madiki mamorekuru emishonga, iyo gene kunyaradza mhedzisiro yeSiRNA mishonga ine yakanyanya kujeka uye kugona.

Musi waNyamavhuvhu 11, 2018, yekutanga siRNA mushonga patisiran (zita rekutengesa Onpattro) yakabvumidzwa neFDA uye yakatanga zviri pamutemo.Ichi ndicho chimwe chezviitiko zvikuru munhoroondo yebudiriro yeRNA interference tekinoroji.Patsiran yakagadziridzwa pamwe chete neAlnylam uye Genzyme, mubatsiri weSanofi.Mushonga we siRNA wekurapa nhaka thyroxine-mediated amyloidosis.Muna 2019, givosiran (zita rekutengesa Givlaari) yakabvumidzwa neFDA sechipiri siRNA mushonga wekurapa acute hepatic porphyria muvakuru.Muna 2020, Alnylam akagadzira mushonga wemhando yekutanga wekurapa vana nevakuru.Lumasiran ine yakakwira oxaluria yakabvumidzwa neFDA.Muna Zvita 2020, Inclisiran, yakabatanidzwa neNovartis neAlnylam yekurapa hypercholesterolemia kana yakasanganiswa dyslipidemia, yakabvumidzwa neEMA.

Aptamer

Nucleic acid aptamers maoligonucleotides anogona kusunga kune akasiyana mamorekuru anotariswa senge madiki organic mamorekuru, DNA, RNA, polypeptides kana mapuroteni ane hukama hwepamusoro uye hutsanana.Kuenzaniswa nemasoja ekudzivirira chirwere, nucleic acid aptamers ane hunhu hwekusanganisa nyore, mutengo wakaderera uye huwandu hwakawanda hwezvinangwa, uye ane mukana wakakura wekushandisa zvinodhaka mukuongororwa kwechirwere, kurapwa nekudzivirira.

Pegaptanib ndiyo yekutanga nucleic acid aptamer drug yakagadzirwa neValeant yekurapa kwekunyorova kwezera remacular degeneration uye yakabvumidzwa neFDA muna 2004. Zvadaro, yakabvumidzwa neEMA nePMDA muna Ndira 2006 naChikunguru 2008 uye yakaenda pamusika.Pegaptanib inhibits angiogenesis kuburikidza nekubatanidzwa kwechimiro chepakati uye vascular endothelial growth factor kuti iwane maitiro ekurapa.Kubva ipapo, yakasangana nemakwikwi kubva kumishonga yakafanana Lucentis, uye chikamu chayo chemusika chakaderera zvakanyanya.

Nucleic acid mishonga yave nzvimbo inopisa mumushonga wekiriniki uye musika mutsva wezvinodhaka nekuda kwemaitiro avo anoshamisa ekurapa uye kupfupika kwekusimudzira.Semushonga uri kubuda, unotarisana nematambudziko uchitarisana nemikana.Nekuda kwehunhu hwayo hwekunze, iwo chaiwo, kugadzikana uye nekubudirira kuendesa nucleic acids zvave nzira huru yekutonga kana oligonucleotides inogona kuve inoshanda zvakanyanya nucleic acid mishonga.Off-chinangwa mhedzisiro yagara iri chinhu chakakosha che nucleic acid zvinodhaka zvisingagoni kuregererwa.Zvisinei, nucleic acid mishonga inogona kukanganisa kutaura kwemajini anokonzera zvirwere kubva pamudzi, uye anogona kuwana kutevedzana kwakananga pane imwe-base-level, iyo ine maitiro e "kurapa chinokonzera uye kurapa zviratidzo".Mukuona kwekusiyana kwezvirwere zvakawanda uye zvakawanda, kurapwa kwemajini chete kunogona kuwana mhedzisiro yekusingaperi.Nekuenderera mberi kwekuvandudza, kukwana uye kufambira mberi kwehunyanzvi hwekuita, nucleic acid zvinodhaka zvinomiririrwa neantisense nucleic acids, siRNA, uye nucleic acid aptamers zvechokwadi ichaisa mafungu matsva mukurapa kwechirwere uye indasitiri yemishonga.

References:

[1] Liu Shaojin, Feng Xuejiao, Wang Junshu, Xiao Zhengqiang, Cheng Pingsheng.Kuongororwa kwemusika kweiyo nucleic acid mishonga munyika yangu uye matanho ekupikisa[J].Chinese Journal of Biological Engineering, 2021, 41(07): 99-109.

[2] Chen Wenfei, Wu Fuhua, Zhang Zhirong, Sun Xun.Kufambira mberi kwekutsvagisa mu pharmacology yemusika nucleic acid zvinodhaka[J].Chinese Journal of Pharmaceuticals, 2020, 51(12): 1487-1496.

[3] Wang Jun, Wang Lan, Lu Jiazhen, Huang Zhen.Ongororo yekubudirira uye kufambira mberi kwekutsvagisa kweinotengeswa nucleic acid mishonga[J].Chinese Journal of New Drugs, 2019, 28(18): 2217-2224.

Nezvemunyori: Sha Luo, mushandi wekuChina wekutsvagisa mushonga uye mushandi webudiriro, parizvino anoshandira kambani hombe yemumba yekutsvagisa zvinodhaka nekusimudzira, uye akazvipira kutsvaga nekuvandudza mishonga mitsva yeChinese.

Zvigadzirwa zvinoenderana:

Cell Direct RT-qPCR kit