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Hamwe niterambere ryiterambere rya tekinoroji ya biologiya, isano iri hagati yimiterere ya gene nudusembwa nindwara byarushijeho gusobanukirwa byimbitse.Acide nucleique yakunze kwitabwaho cyane kubera ubushobozi bukomeye bwo gukoresha mugupima no kuvura indwara.Imiti ya acide nucleique bivuga ibihimbano byakozwe na ADN cyangwa RNA hamwe nibikorwa byo kuvura indwara.Imiti nkiyi irashobora gukora muburyo butaziguye indwara zitera indwara cyangwa mRNA itera indwara, kandi ikagira uruhare mukuvura indwara kurwego rwa gen.Ugereranije n'imiti mito ya molekile gakondo hamwe nibiyobyabwenge bya antibody, imiti ya acide nucleique irashobora kugenga imvugo ya gen zitera indwara ziva mumuzi, kandi zikagira ibiranga "kuvura ibimenyetso no gukiza intandaro".Imiti ya acide nucleique nayo ifite ibyiza bigaragara nko gukora neza, uburozi buke, hamwe nuburyo bwihariye.Kuva imiti ya mbere ya nucleic aside fomivirsen sodium yatangizwa mu 1998, imiti myinshi ya acide nucleic yemerewe kuvurwa.

Imiti ya nucleic acide kuri ubu ku isoko kwisi yose harimo aside antisense nucleic aside (ASO), RNA ntoya (siRNA), hamwe na aptamers acide nucleic.Usibye acide nucleic aptamers (ishobora kurenga 30 nucleotide), imiti ya acide nucleique mubisanzwe ni oligonucleotide igizwe na nucleotide 12 kugeza 30, izwi kandi nk'imiti ya oligonucleotide.Byongeye kandi, miRNAs, ribozymes na deoxyribozymes nazo zagaragaje agaciro gakomeye mu iterambere mu kuvura indwara zitandukanye.Imiti ya acide nucleique yabaye imwe mubice bitanga icyizere mubushakashatsi no guteza imbere biomedicine muri iki gihe.

Ingero z'imiti ya nucleic yemewe

asdsada

Antisense nucleic aside

Ikoranabuhanga rya Antisense nubuhanga bushya bwo guteza imbere ibiyobyabwenge bushingiye ku ihame ryo kuzuzanya kwa Watson-Crick, ukoresheje ibice byihariye bya ADN cyangwa RNA byuzuzanya byakozwe mu buryo bwa gihanga cyangwa bigahuzwa n’ibinyabuzima kugira ngo bigenzure neza imvugo ya gen.Antisense nucleic aside ifite urutonde rwibanze rwuzuzanya nintego ya RNA kandi irashobora kuyihuza byumwihariko.Acide nucleic acide muri rusange harimo ADN antisense, antisense RNA na ribozymes.Muri byo, bitewe n'ibiranga umutekano muke hamwe nigiciro gito cya ADN antisense, ADN antisense ifite umwanya wambere mubushakashatsi burimo gukorwa no gukoresha imiti ya aside irike nucleis.

Sodium ya Fomivirsen (izina ry'ubucuruzi Vitravene) yakozwe na Ionis Novartis.Muri Kanama 1998, FDA yemeye kuyivura cytomegalovirus retinitis ku barwayi badafite ubudahangarwa (cyane cyane abarwayi ba sida), ibaye imiti ya mbere ya acide nucleique yagurishijwe ku isoko.Fomivirsen ibuza poroteyine igice cya CMV guhuza na mRNA yihariye (IE2), bityo ikagenga imvugo ya virusi kugirango igere ku ngaruka zo kuvura.Icyakora, kubera ko hagaragaye imiti igabanya ubukana bwa virusi itera SIDA, yagabanije cyane umubare w’abarwayi, mu 2002 na 2006, Novartis yahagaritse uburenganzira bw’isoko ry’ibiyobyabwenge bya Fomivirsen mu Burayi no muri Amerika, kandi ibicuruzwa byahagaritswe ku isoko.

Sodium ya Mipomersen (izina ry'ubucuruzi Kynamro) ni imiti ya ASO yakozwe na sosiyete y'Abafaransa Genzyme.Muri Mutarama 2013, FDA yemeje kuvura hypercholesterolemia yo mu muryango.Mipomersen ibuza imvugo ya poroteyine ya ApoB-100 (apolipoproteine) ihuza na ApoB-100mRNA, bityo bikagabanya cyane cholesterol ya lipoprotein nkeya ya lipoprotein, lipoprotein nkeya n’ibindi bipimo, ariko kubera ingaruka mbi nk’uburozi bw’umwijima, ku ya 13 Ukuboza 2012 Kuri uwo munsi, EMA nayo yanze gusaba uruhushya rwo kugurisha.

Muri Nzeri 2016, Eteplirsen (izina ry'ubucuruzi Exon 51) yakozwe na Sarepta mu kuvura indwara ya Duchenne muscular dystrofiya (DMD) yemejwe na FDA.Abarwayi ba DMD ntibashobora kwerekana proteine ​​ikora anti-atrophique kubera ihinduka ryimiterere ya DMD mumubiri.Eteplirsen ihuza cyane na exon 51 ya pre-messenger RNA (Pre-mRNA) ya poroteyine, ikuraho exon 51, kandi igarura genes zimwe na zimwe zo hasi.

Nusinersen ni umuti wa ASO wakozwe na Spinraza mu kuvura indwara y’imitsi y’umugongo kandi wemejwe na FDA ku ya 23 Ukuboza 2016. Muri 2018, Inotesen yakozwe na Tegsedi mu rwego rwo kuvura abakurambere bakomoka kuri transthyretin amyloidose yemewe na FDA.Muri 2019, Golodirsen, yakozwe na Sarepta mu kuvura dystrofiya ya Duchenne, yemejwe na FDA.Ifite uburyo bumwe bwibikorwa nka Eteplirsen, kandi aho ikorera iba exon 53. Muri uwo mwaka, Volanesorsen, yatejwe imbere na Ionisand Akcea mu kuvura hyperchylomicronemia yo mu muryango, yemejwe n’ikigo cy’ubuvuzi cy’Uburayi (EMA).Volanesorsen igenga metabolism ya triglyceride ibuza umusaruro wa apolipoproteine ​​C-but, ariko kandi ifite ingaruka zo kugabanya urugero rwa platel.

 

Defibrotide ni oligonucleotide ivanze nibintu bya plasmin byakozwe na Jazz.Irimo ADN 90% ya ADN imwe imwe na 10% ADN ikubye kabiri.Byemejwe na EMA mu 2013 hanyuma byemezwa na FDA yo kuvura imitsi ikabije y'umwijima.Indwara idasanzwe.Defibrotide irashobora kongera ibikorwa bya plasmin, ikongera plasminogen ikora, igateza imbere kugenga trombomoduline, no kugabanya imvugo yibintu bya Wil Wilbrabrand hamwe na inhibitori ya plasminogen kugirango igere ku ngaruka zo kuvura

siRNA     

siRNA ni agace gato ka RNA ifite uburebure bwihariye hamwe nurutonde rwakozwe mugukata intego RNA.Izi siRNAs zirashobora cyane cyane gutesha agaciro intego ya mRNA no kugera ku ngaruka zo gucecekesha gene.Ugereranije n’imiti mito ya molekile ntoya, ingaruka zo gucecekesha gene yimiti ya siRNA ifite umwihariko kandi neza.

Ku ya 11 Kanama 2018, ibiyobyabwenge bya siRNA bya mbere patisiran (izina ry'ubucuruzi Onpattro) byemejwe na FDA biratangizwa ku mugaragaro.Iyi ni imwe mu ntambwe zikomeye mu mateka yiterambere rya tekinoroji ya RNA.Patisiran yatejwe imbere na Alnylam na Genzyme, ishami rya Sanofi.Numuti wa siRNA wo kuvura amyloidose yumurage wa thyroxine.Muri 2019, givosiran (izina ry'ubucuruzi Givlaari) yemejwe na FDA nk'umuti wa kabiri wa siRNA wo kuvura porphiriya ikabije ya hepatike ku bantu bakuru.Muri 2020, Alnylam yakoze imiti y'ibanze yo kuvura abana ndetse n'abantu bakuru.Lumasiran hamwe na oxaluria nyinshi byemejwe na FDA.Ukuboza 2020, Inclisiran, yakozwe na Novartis na Alnylam mu kuvura hypercholesterolemia ikuze cyangwa ivanze na dyslipidemiya ivanze, byemejwe na EMA.

Aptamer

Nucleic acide aptamers ni oligonucleotide ishobora guhuza na molekile zitandukanye zigamije nka molekile ntoya, ADN, RNA, polypeptide cyangwa proteyine zifitanye isano ryinshi kandi ryihariye.Ugereranije na antibodies, aptamers acide nucleic ifite ibiranga synthesis yoroshye, igiciro gito hamwe nintego zitandukanye, kandi bifite amahirwe menshi yo gukoresha ibiyobyabwenge mugupima indwara, kuvura no kwirinda.

Pegaptanib niwo muti wa mbere wa nucleic aside aptamer yakozwe na Valeant mu rwego rwo kuvura indwara ya macula yatewe n'imyaka itose kandi byemejwe na FDA mu 2004. Nyuma, byemejwe na EMA na PMDA muri Mutarama 2006 na Nyakanga 2008 maze bijya ku isoko.Pegaptanib ibuza angiogenez binyuze mu guhuza imiterere yimiterere niterambere ryamaraso ya endoteliyale kugirango igere ku ngaruka zo kuvura.Kuva icyo gihe, yahuye n’irushanwa rituruka ku biyobyabwenge bisa na Lucentis, kandi umugabane wacyo ku isoko wagabanutse cyane.

Imiti ya acide nucleique yabaye ahantu hashyushye mumiti yubuvuzi nisoko rishya ryibiyobyabwenge kubera ingaruka zidasanzwe zo gukiza hamwe niterambere ryigihe gito.Nkumuti ugaragara, uhura nibibazo mugihe uhuye namahirwe.Bitewe nibiranga imiterere yihariye, umwihariko, ituze hamwe nogutanga neza acide nucleic byabaye ingingo nyamukuru yo gusuzuma niba oligonucleotide ishobora guhinduka imiti ya acide nucleique.Ingaruka zitari intego zahoze ari ingingo yingenzi yimiti ya nucleic aside idashobora kwirengagizwa.Nyamara, imiti ya nucleic aside irashobora kugira ingaruka kumagambo ya gen zitera indwara ziva mumuzi, kandi irashobora kugera kumurongo wihariye murwego rumwe, rufite ibiranga "kuvura intandaro no kuvura ibimenyetso".Urebye itandukaniro ryindwara nyinshi kandi nyinshi, kuvura genetike gusa bishobora kugera kubisubizo bihoraho.Hamwe nogukomeza gutera imbere, gutunganirwa niterambere ryikoranabuhanga rifitanye isano, imiti ya acide nucleique ihagarariwe na acide anticense nucleic acide, siRNA, na aptamers acide nucleic rwose bizashyiraho umurongo mushya mubuvuzi bwindwara ninganda zimiti.

RIbyifuzo:

[1] Liu Shaojin, Feng Xuejiao, Wang Junshu, Xiao Zhengqiang, Cheng Pingsheng.Isesengura ryisoko ryimiti ya acide nucleic mugihugu cyanjye hamwe ningamba zo guhangana [J].Ikinyamakuru cyo mu Bushinwa cy’ubuhanga bw’ibinyabuzima, 2021, 41 (07): 99-109.

[2] Chen Wenfei, Wu Fuhua, Zhang Zhirong, Sun Xun.Iterambere ryubushakashatsi muri farumasi yimiti ya acide nucleic yagurishijwe [J].Ikinyamakuru cyo mu Bushinwa cy’imiti, 2020, 51 (12): 1487-1496.

[3] Wang Jun, Wang Lan, Lu Jiazhen, Huang Zhen.Isesengura ryimikorere niterambere ryubushakashatsi bwibiyobyabwenge bya acide nucleic bicuruzwa [J].Ikinyamakuru cyo mu Bushinwa cy’ibiyobyabwenge bishya, 2019, 28 (18): 2217-2224.

Kubyerekeye umwanditsi: Sha Luo, umushakashatsi w’ubuvuzi n’iterambere mu Bushinwa, kuri ubu akora mu kigo kinini cy’ubushakashatsi n’iterambere ry’ibiyobyabwenge mu gihugu, kandi yiyemeje gukora ubushakashatsi no guteza imbere imiti mishya y’Ubushinwa.

Ibicuruzwa bifitanye isano:

Akagari ka RT-qPCR kit


Igihe cyo kohereza: Ugushyingo-19-2021