Ka nts'etsopele e tsoelang pele ea theknoloji ea baeloji ea limolek'hule, kamano pakeng tsa liphetoho tsa lefutso le bofokoli le mafu e fumane kutloisiso e tebileng haholoanyane.Li-nucleic acid li hohetse tlhokomelo e kholo ka lebaka la bokhoni ba tsona bo boholo ba ho sebelisoa tlhahlobong le kalafong ea mafu.Lithethefatsi tsa Nucleic acid li bua ka likhechana tsa DNA kapa tsa RNA tse entsoeng ka maiketsetso tse nang le mesebetsi ea kalafo ea mafu.Lithethefatsi tse joalo li ka sebetsa ka kotloloho ho liphatsa tsa lefutso tse bakang mafu kapa li-mRNA tse bakang mafu, 'me tsa bapala karolo ea ho phekola mafu ka liphatsa tsa lefutso.Ha ho bapisoa le lithethefatsi tse tloaelehileng tsa molek'hule le lithethefatsi tsa antibody, lithethefatsi tsa nucleic acid li ka laola polelo ea liphatsa tsa lefutso tse bakang mafu ho tloha motsong, 'me li na le litšobotsi tsa "ho phekola matšoao le ho phekola sesosa".Lithethefatsi tsa Nucleic acid le tsona li na le melemo e hlakileng joalo ka ts'ebetso e phahameng, chefo e tlase le maemo a holimo.Ho tloha ha sethethefatsi sa pele sa "nucleic acid" sa fomivirsen sodium se qalisoa ka 1998, litlhare tse ngata tsa nucleic acid li amohetsoe bakeng sa kalafo ea bongaka.
Lithethefatsi tsa li-nucleic acid hajoale tse 'marakeng lefatšeng ka bophara li kenyelletsa antisense nucleic acid (ASO), li-antisense nucleic acid (ASO), tse kenang lipakeng tse nyane tsa RNA (siRNA), le li-aptamers tsa nucleic acid.Ntle le li-aptamers tsa nucleic acid (tse ka fetang li-nucleotide tse 30), lithethefatsi tsa nucleic acid hangata li oligonucleotide tse entsoeng ka li-nucleotide tse 12 ho isa ho tse 30, tse tsejoang hape e le oligonucleotide lithethefatsi.Ho feta moo, li-miRNA, li-ribozyme le li-deoxyribozyme le tsona li bontšitse boleng bo boholo ba nts'etsopele kalafong ea mafu a fapaneng.Lithethefatsi tsa Nucleic acid li fetohile tse ling tsa masimo a tšepisang ka ho fetisisa lipatlisisong le nts'etsopele ea biomedicine kajeno.
Mehlala ea litlhare tse lumelletsoeng tsa nucleic acid
Antisense nucleic acid
Theknoloji ea Antisense ke thekenoloji e ncha ea nts'etsopele ea lithethefatsi e thehiloeng ho molao-motheo oa tlatsetso ea Watson-Crick, e sebelisang likaroloana tsa DNA kapa tsa RNA tse entsoeng ka maiketsetso kapa tse entsoeng ke 'mele ho laola ka ho khetheha polelo ea liphatsa tsa lefutso.Antisense nucleic acid e na le tatellano ea motheo e tlatsanang le sepheo sa RNA 'me e ka e tlama ka ho khetheha.Antisense nucleic acid hangata e kenyelletsa antisense DNA, antisense RNA le ribozymes.Har'a bona, ka lebaka la litšobotsi tsa botsitso bo phahameng le theko e tlaase ea DNA ea antisense, DNA ea antisense e nka boemo bo ka sehloohong lipatlisisong tsa morao-rao le tšebeliso ea lithethefatsi tsa antisense nucleic acid.
Fomivirsen sodium (lebitso la khoebo Vitravene) e entsoe ke Ionis Novartis.Ka Phato 1998, FDA e ile ea e amohela bakeng sa kalafo ea cytomegalovirus retinitis ho bakuli ba nang le immunocompromised (haholo-holo bakuli ba AIDS), ea fetoha moriana oa pele oa nucleic acid ho rekisoa.Fomivirsen e thibela karolo e itseng ea protheine ea CMV ka ho tlama ho mRNA e itseng (IE2), kahoo e laola polelo ea liphatsa tsa lefutso tsa kokoana-hloko ho finyella liphello tsa phekolo.Leha ho le joalo, ka lebaka la ho hlaha ha kalafo e sebetsang hantle haholo ea li-antiretroviral, e fokolitseng palo ea bakuli haholo, ka 2002 le 2006, Novartis e ile ea hlakola tumello ea 'maraka ea lithethefatsi tsa Fomivirsen Europe le United States ka ho latellana,' me sehlahisoa se emisitsoe 'marakeng.
Mipomersen sodium (lebitso la khoebo Kynamro) ke moriana oa ASO o entsoeng ke k'hamphani ea Fora Genzyme.Ka Pherekhong 2013, FDA e e amohetse bakeng sa kalafo ea homozygous family hypercholesterolemia.Mipomersen e thibela polelo ea ApoB-100 protheine (apolipoprotein) ka ho tlama ApoB-100mRNA, ka tsela eo e fokotsa haholo batho ba low-density lipoprotein cholesterol, low-density lipoprotein le matšoao a mang, empa ka lebaka la litla-morao tse kang chefo ea sebete, December 13, 2012 le laesense ea thekiso ea lithethefatsi e hanne ka letsatsi le tšoanang la EMA.
Ka Loetse 2016, Eteplirsen (lebitso la khoebo Exon 51) e ntlafalitsoeng ke Sarepta bakeng sa kalafo ea Duchenne muscular dystrophy (DMD) e ile ea amoheloa ke FDA.Bakuli ba DMD ha ba khone ho bua ka mokhoa o tloaelehileng oa protheine ea anti-atrophic ka lebaka la liphetoho tsa lefutso la DMD 'meleng.Eteplirsen e tlama ka ho khetheha ho exon 51 ea pre-messenger RNA (Pre-mRNA) ea protheine, e tlosa exon 51, 'me e tsosolosa liphatsa tsa lefutso tse ling tsa tlaase Polelo e tloaelehileng ea, ho ngoloa le phetolelo ho fumana karolo ea dystrophin, e le ho finyella phello ea phekolo.
Nusinersen ke lithethefatsi tsa ASO tse entsoeng ke Spinraza bakeng sa phekolo ea mokokotlo oa mokokotlo oa mokokotlo 'me o ile oa amoheloa ke FDA ka December 23, 2016. Ka 2018, Inotesen e entsoeng ke Tegsedi bakeng sa phekolo ea lefutso la batho ba baholo ba transthyretin amyloidosis e ile ea amoheloa ke FDA.Ka 2019, Golodirsen, e ntlafalitsoeng ke Sarepta bakeng sa kalafo ea Duchenne muscular dystrophy, e ile ea amoheloa ke FDA.E na le mokhoa o tšoanang le oa Eteplirsen, 'me sebaka sa eona sa ts'ebetso se fetoha exon 53. Selemong sona seo, Volanesorsen, e kopantsoeng ke Ionisand Akcea bakeng sa phekolo ea hyperchylomicronemia ea malapa, e ile ea amoheloa ke European Medicines Agency (EMA).Volanesorsen e laola metabolism ea triglyceride ka ho thibela tlhahiso ea apolipoprotein C-Ⅲ, empa e boetse e na le litlamorao tsa ho theola maemo a platelet.
Defibrotide ke motsoako oa oligonucleotide o nang le thepa ea plasmin e entsoeng ke Jazz.E na le 90% ea DNA ea khoele e le 'ngoe le 10% ea DNA e habeli.E amohetsoe ke EMA ka 2013 mme kamora moo ea amoheloa ke FDA bakeng sa kalafo ea methapo e matla ea sebete.Boloetse bo sa tsitsang.Defibrotide e ka eketsa ts'ebetso ea plasmin, ea eketsa activator ea plasminogen, ea phahamisa taolo ea thrombomodulin, le ho fokotsa polelo ea von Willebrand factor le plasminogen activator inhibitors ho fihlela litlamorao tsa kalafo.
siRNA
siRNA ke sekhechana se senyenyane sa RNA se nang le bolelele bo itseng le tatellano e hlahisoang ka ho seha sepheo sa RNA.Li-siRNA tsena li ka susumetsa ka kotloloho ho senyeha ha sepheo sa mRNA le ho fihlela litlamorao tsa ho khutsisa liphatsa tsa lefutso.Ha ho bapisoa le lithethefatsi tsa molek'hule tse nyane tsa lik'hemik'hale, phello ea ho khutsisa liphatsa tsa lefutso ea lithethefatsi tsa siRNA e na le ts'ebetso e phahameng le ts'ebetso e phahameng.
Ka Phato 11, 2018, sethethefatsi sa pele sa siRNA patisiran (lebitso la khoebo Onpattro) se ile sa amoheloa ke FDA mme sa tsebisoa ka molao.Ena ke e 'ngoe ea liketsahalo tsa bohlokoa nalaneng ea nts'etsopele ea theknoloji ea tšitiso ea RNA.Patsiran e entsoe ka kopanelo ke Alnylam le Genzyme, e leng setsi sa Sanofi.Ke moriana oa siRNA bakeng sa kalafo ea lefutso la thyroxine-mediated amyloidosis.Ka 2019, givosiran (lebitso la khoebo la Givlaari) e ile ea amoheloa ke FDA e le moriana oa bobeli oa siRNA bakeng sa kalafo ea acute hepatic porphyria ho batho ba baholo.Ka 2020, Alnylam e ile ea theha sethethefatsi sa mantlha sa mofuta oa I bakeng sa kalafo ea bana le batho ba baholo.Lumasiran e nang le oxaluria e phahameng e amohetsoe ke FDA.Ka December 2020, Inclisiran, e kopantsoeng ke Novartis le Alnylam bakeng sa kalafo ea hypercholesterolemia ea batho ba baholo kapa dyslipidemia e tsoakiloeng, e ile ea amoheloa ke EMA.
Aptamer
Nucleic acid aptamers ke li-oligonucleotide tse ka tlamang limolek'hule tse fapaneng tse shebiloeng joalo ka limolek'hule tse nyane tsa organic, DNA, RNA, polypeptides kapa liprotheine tse nang le kamano e phahameng le e ikhethang.Ha ho bapisoa le li-antibodies, li-aptamers tsa nucleic acid li na le litšobotsi tsa motsoako o bonolo, theko e tlaase le lipakane tse ngata, 'me li na le monyetla o moholo oa ho sebelisa lithethefatsi ho hlahloba mafu, phekolo le thibelo.
Pegaptanib ke lithethefatsi tsa pele tsa nucleic acid aptamer tse entsoeng ke Valeant bakeng sa phekolo ea ho senyeha ha macular tse amanang le lilemo tse metsi 'me e ile ea amoheloa ke FDA ka 2004. Ka mor'a moo, e ile ea amoheloa ke EMA le PMDA ka January 2006 le July 2008 'me ea tsoela pele' marakeng.Pegaptanib e thibela angiogenesis ka ho kopanya sebopeho sa sebaka le vascular endothelial growth factor ho finyella liphello tsa phekolo.Ho tloha ka nako eo, e 'nile ea kopana le tlhōlisano ea lithethefatsi tse tšoanang Lucentis,' me karolo ea eona ea 'maraka e theohile haholo.
Lithethefatsi tsa Nucleic acid e se e le sebaka se chesang 'marakeng oa lithethefatsi tsa bongaka le 'marakeng o mocha oa lithethefatsi ka lebaka la phello e makatsang ea pholiso le potoloho e khuts'oane ea nts'etsopele.Joaloka sethethefatsi se hlahang, se tobana le mathata ha se ntse se tobane le menyetla.Ka lebaka la litšoaneleho tsa eona tsa kantle ho naha, boits'oaro, botsitso le phano e sebetsang ea li-nucleic acid e fetohile mokhoa o ka sehloohong oa ho ahlola hore na oligonucleotide e ka fetoha lithethefatsi tse sebetsang haholo tsa nucleic acid.Liphello tse sa lebelloang esale e le ntlha ea bohlokoa ea lithethefatsi tsa nucleic acid tse ke keng tsa hlokomolohuoa.Leha ho le joalo, lithethefatsi tsa nucleic acid li ka ama polelo ea liphatsa tsa lefutso tse bakang mafu ho tloha motso, 'me li ka finyella tatellano e tobileng ea boemo bo le bong, e nang le litšobotsi tsa "ho phekola sesosa le ho phekola matšoao".Ka lebaka la ho fapana ha mafu a mangata, ke phekolo ea liphatsa tsa lefutso feela e ka finyellang liphello tse sa feleng.Ka ntlafatso e tsoelang pele, phetheho le tsoelo-pele ea theknoloji e amanang le eona, lithethefatsi tsa nucleic acid tse emeloang ke antisense nucleic acids, siRNA, le li-aptamers tsa nucleic acid li tla hlahisa leqhubu le lecha la phekolo ea mafu le indasteri ea meriana.
Rlitlhaloso:
[1] Liu Shaojin, Feng Xuejiao, Wang Junshu, Xiao Zhengqiang, Cheng Pingsheng.Tlhahlobo ea 'maraka ea lithethefatsi tsa nucleic acid naheng ea heso le mehato ea ho thibela [J].Chinese Journal of Biological Engineering, 2021, 41(07): 99-109.
[2] Chen Wenfei, Wu Fuhua, Zhang Zhirong, Sun Xun.Tsoelo-pele ea lipatlisiso ho pharmacology ea lithethefatsi tse rekisoang tsa nucleic acid[J].Chinese Journal of Pharmaceuticals, 2020, 51(12): 1487-1496.
[3] Wang Jun, Wang Lan, Lu Jiazhen, Huang Zhen.Tlhahlobo ea katleho le tsoelo-pele ea lipatlisiso tsa lithethefatsi tse rekisoang tsa nucleic acid[J].Koranta ea China ea Lithethefatsi tse Ncha, 2019, 28(18): 2217-2224.
Mabapi le mongoli: Sha Luo, mosebeletsi oa lipatlisiso le nts'etsopele ea meriana ea Sechaena, hajoale o sebeletsa k'hamphani e kholo ea lapeng ea lipatlisiso le nts'etsopele ea lithethefatsi, 'me o ikemiselitse ho etsa lipatlisiso le nts'etsopele ea meriana e mecha ea Machaena.
Lihlahisoa tse amanang:
Nako ea poso: Nov-19-2021
