Inkomoko: Micro yubuvuzi
Nyuma y’icyorezo cya COVID-19, inkingo ebyiri za mRNA zemejwe vuba kugira ngo zimenyekanishe, zikaba zarushijeho kwita ku iterambere ry’imiti ya aside nucleique.Mu myaka yashize, imiti myinshi ya acide nucleic ifite ubushobozi bwo kuba imiti igabanya ubukana yashyize ahagaragara amakuru y’ubuvuzi, ikubiyemo indwara z'umutima na metabolike, indwara z'umwijima, n'indwara zitandukanye zidasanzwe.Biteganijwe ko imiti ya acide nucleique izahinduka imiti mito ya molekile ikurikira.Ubwoko bwa gatatu bunini bwibiyobyabwenge.
Icyiciro cyibiyobyabwenge bya acide
Acide nucleique ni ibinyabuzima bya macromolecular biologique byakozwe na polymerisation ya nucleotide nyinshi, kandi nikimwe mubintu byingenzi byubuzima.Imiti ya acide nucleique ni oligoribonucleotide itandukanye (RNA) cyangwa oligodeoxyribonucleotide (ADN) ifite imirimo itandukanye, ishobora gukora muburyo butaziguye ingirabuzimafatizo zitera indwara cyangwa intego za mRNAs zo kuvura indwara kurwego rwa gene Uruhare rwa.
Process Synthesis inzira kuva ADN kugeza RNA kugeza proteine (Inkomoko yishusho: bing)
Kugeza ubu, imiti nyamukuru ya acide nucleique irimo antisense nucleic aside (ASO), RNA ntoya (siRNA), microRNA (miRNA), ntoya ikora RNA (saRNA), intumwa RNA (mRNA), aptamer, na ribozyme., Antibody nucleic aside conjugated imiti (ARC), nibindi
Usibye mRNA, ubushakashatsi niterambere ryibindi biyobyabwenge bya nucleic aside nabyo byitabweho cyane mumyaka yashize.Muri 2018, hemejwe imiti ya mbere ya siRNA ku isi (Patisiran), kandi niwo muti wa mbere wa nucleic aside wakoresheje uburyo bwo gutanga LNP.Mu myaka yashize, umuvuduko w isoko ryimiti ya nucleic aside nayo yihuse.Muri 2018-2020 honyine, hari imiti 4 ya siRNA, Imiti itatu ya ASO yemejwe (FDA na EMA).Mubyongeyeho, Aptamer, miRNA nizindi nzego nazo zifite imiti myinshi murwego rwubuvuzi.
Ibyiza nibibazo byimiti ya acide nucleic
Kuva mu myaka ya za 1980, ubushakashatsi no guteza imbere imiti mishya ishingiye ku ntego byagutse buhoro buhoro, kandi havumbuwe imiti myinshi mishya;imiti gakondo ya molekile ntoya hamwe nibiyobyabwenge bya antibody byombi bigira ingaruka kumiti muguhuza poroteyine.Intungamubiri za poroteyine zirashobora kuba Enzymes, reseptors, imiyoboro ya ion, nibindi.
Nubwo imiti ya molekile ntoya ifite ibyiza byo gukora byoroshye, kuyobora umunwa, imiti myiza ya farumasi, hamwe no kunyura mumyanya ndangagitsina, iterambere ryabo riterwa no kunywa ibiyobyabwenge byintego (kandi niba poroteyine yintego ifite imiterere yubunini nubunini).Ubujyakuzimu, polarite, nibindi);ukurikije ingingo yo muri Kamere2018, 3.000 gusa muri proteine ~ 20.000 zashyizweho na genome yumuntu zishobora kuba imiti, naho 700 gusa ni zo zifite imiti ihuye nayo (muri chimique ntoya ya molekile).
Inyungu nini yimiti ya acide nucleique nuko imiti itandukanye ishobora gutezwa imbere gusa muguhindura urwego shingiro rwa acide nucleic.Ugereranije nibiyobyabwenge bikora kurwego rwa poroteyine gakondo, inzira yiterambere ryayo iroroshye, ikora neza, kandi ibinyabuzima byihariye;ugereranije no kuvura ADN yo mu rwego rwa ADN, imiti ya acide nucleic ntabwo ifite ibyago byo guhuza gene kandi iroroshye guhinduka mugihe cyo kuvura.Imiti irashobora guhagarikwa mugihe nta muti ukenewe.
Imiti ya acide nucleique ifite ibyiza bigaragara nkibisobanuro bihanitse, imikorere myiza ningaruka ndende.Nyamara, hamwe nibyiza byinshi hamwe niterambere ryihuse, imiti ya acide nucleic nayo ihura nibibazo bitandukanye.
Imwe muriyo ni RNA ihindura kugirango iteze imbere imiti ya acide nucleic no kugabanya ubudahangarwa bw'umubiri.
Iya kabiri ni iterambere ryabatwara kugirango barebe ko RNA ihagaze neza mugihe cyo kohereza aside nucleic hamwe nibiyobyabwenge bya acide nucleic kugirango bigere ku ngirabuzimafatizo / ingingo zigenewe;
Icya gatatu ni ugutezimbere uburyo bwo gutanga ibiyobyabwenge.Nigute ushobora kunoza uburyo bwo gutanga ibiyobyabwenge kugirango ugere ku ngaruka imwe hamwe na dosiye nkeya.
Guhindura imiti imiti ya nucleic
Imiti ya acide nucleic aside ikeneye gutsinda inzitizi nyinshi kugirango yinjire mumubiri kugirango igire uruhare.Izi mbogamizi kandi zateje ingorane mugutezimbere imiti ya acide nucleic.Ariko, hamwe niterambere ryikoranabuhanga rishya, bimwe mubibazo bimaze gukemurwa no guhindura imiti.Kandi intambwe mu ikorana buhanga rya sisitemu yagize uruhare runini mugutezimbere imiti ya acide nucleic.
Guhindura imiti birashobora kongera ubushobozi bwimiti ya RNA yo kurwanya iyangirika rya endogenous endonuclease na exonuclease, kandi bikazamura cyane imikorere yibiyobyabwenge.Ku miti ya siRNA, guhindura imiti birashobora kandi kongera uburyo bwo guhitamo imirongo ya antisense kugirango igabanye ibikorwa bya RNAi bitagamije, kandi ihindure imiterere yumubiri na chimique kugirango yongere ubushobozi bwo gutanga.
1. Guhindura imiti yisukari
Mugihe cyambere cyo guteza imbere ibiyobyabwenge bya nucleic aside, ibice byinshi bya acide nucleique byerekanaga ibikorwa byiza byibinyabuzima muri vitro, ariko ibikorwa byabo muri vivo byagabanutse cyane cyangwa byatakaye rwose.Impamvu nyamukuru nuko acide nucleic idahinduwe ivunika byoroshye na enzymes cyangwa ibindi bintu bya endogenous mumubiri.Guhindura imiti yisukari ikubiyemo cyane cyane guhindura hydroxyl yumwanya wa 2 (2'OH) yisukari kuri mikorerexy (2'OMe), fluorine (F) cyangwa (2'MOE).Ihinduka rirashobora kongera ibikorwa no guhitamo, kugabanya ingaruka zitari intego, no kugabanya ingaruka.
Guhindura imiti yisukari (isoko yishusho: reba 4)
2. Guhindura fosifori acide skeleton
Guhindura imiti ikoreshwa cyane muguhindura umugongo wa fosifate ni fosifori, ni ukuvuga, ogisijeni idafite ikiraro muri fosifate yumugongo wa nucleotide isimbuzwa sulfure (PS modification).Guhindura PS birashobora kurwanya iyangirika rya nuclease no kongera imikoranire yimiti ya acide nucleic na proteyine za plasma.Ubushobozi bwo guhuza, gabanya igipimo cyo gukuraho impyiko no kongera igice cyubuzima.
Guhindura fosifori (isoko y'amashusho: reba 4)
Nubwo PS ishobora kugabanya isano ya acide nucleic na genes zigamije, guhindura PS ni hydrophobique kandi ihamye, bityo rero iracyahinduka cyane muguhuza acide nucleic acide na acide nucleic acide.
3. Guhindura impeta igizwe nabantu batanu ba ribose
Guhindura impeta igizwe n'abantu batanu ba ribose byitwa guhindura imiti yo mu gisekuru cya gatatu, harimo aside nucleic aside ifunze nucleic aside BNAs, peptide nucleic aside PNA, fosiforiodiamide morpholino oligonucleotide PMO, izi mpinduka zirashobora kurushaho kuzamura imiti ya acide nucleique Kurwanya nuclease, kunoza ubumwe no kwihariye, nibindi.
4. Ibindi byahinduwe byimiti
Mu rwego rwo gukemura ibibazo bitandukanye by’imiti ya acide nucleique, abashakashatsi mubisanzwe bahindura kandi bagahindura kubishingwe nu munyururu wa nucleotide kugirango bongere ituze ryimiti ya acide nucleique.
Kugeza ubu, imiti yose yibasira RNA yemejwe na FDA ni imashini yakozwe na chimique igereranya RNA, ishyigikira akamaro ko guhindura imiti.Oligonucleotide imwe-imwe igizwe nicyiciro cyihariye cyo guhindura imiti itandukanye gusa, ariko byose bifite imiterere-karemano yumubiri na chimique, bityo ikaba ifite imiti ihuriweho na biologiya.
Gutanga no kuyobora imiti ya acide nucleic
Imiti ya acide nucleique ishingiye gusa ku guhindura imiti iracyangirika vuba vuba mu maraso, ntabwo byoroshye kwegeranya mu ngingo zifatika, kandi ntibyoroshye kwinjira neza mu ngirabuzimafatizo kugira ngo igere aho ikorera muri cytoplazme.Kubwibyo, imbaraga za sisitemu yo gutanga zirakenewe.
Kugeza ubu, ibiyobyabwenge bya nucleic aside bigabanyijemo ahanini virusi na virusi.Iyambere irimo virusi ifitanye isano na adenovirus (AAV), lentivirus, adenovirus na retrovirus, nibindi. Harimo abatwara lipide, imitsi nibindi nkibyo.Urebye imiti igurishwa, virusi ya virusi hamwe nabatwara lipide bakuze cyane mugutanga imiti ya mRNA, mugihe imiti mito ya acide nucleic ikoresha abatwara ibintu byinshi cyangwa urubuga rwikoranabuhanga nka liposomes cyangwa GalNAc.
Kugeza ubu, imiti myinshi ya nucleotide, harimo imiti ya acide nucleic yemewe hafi ya yose, yagiye ikorerwa mu karere, nk'amaso, uruti rw'umugongo, n'umwijima.Nucleotide mubisanzwe ni hydrophilique polyanion nini, kandi uyu mutungo bivuze ko bidashobora kunyura byoroshye muri plasma membrane.Muri icyo gihe, imiti ivura ishingiye kuri oligonucleotide ntishobora kwambuka inzitizi y'amaraso n'ubwonko (BBB), bityo rero kugeza muri sisitemu yo hagati (CNS) ni ikibazo gikurikira ku miti ya acide nucleique.
Birakwiye ko tumenya ko igishushanyo mbonera cya acide nucleic hamwe no guhindura aside nucleic kuri ubu aribyo byibandwaho nabashakashatsi murwego.Kugirango uhindure imiti, acide nucleic acide ya chimique, igishushanyo mbonera cya acide nucleique idasanzwe cyangwa igishushanyo mbonera, imiterere ya acide nucleic, ubwubatsi bwa vector, uburyo bwa synthesis nucleic, nibindi nibindi.
Fata urugero rushya rwa coronavirus.Kubera ko RNA yayo ari ikintu kibaho muburyo busanzwe muri kamere, "RNA ya coronavirus nshya" ubwayo ntishobora guhabwa patenti.Ariko, niba umushakashatsi wa siyansi yitandukanije cyangwa akuramo RNA cyangwa ibice bitazwi mu ikoranabuhanga muri coronavirus nshya ku nshuro ya mbere akabishyira mu bikorwa (urugero, kubihindura urukingo), noneho aside nucleic ndetse n’urukingo byombi bishobora guhabwa uburenganzira bw’ipatanti hakurikijwe amategeko.Byongeye kandi, molekile ya acide nucleique yakozwe mubushakashatsi bwa coronavirus nshya, nka primers, probe, sgRNA, vectors, nibindi, byose nibintu byemewe.
Ijambo risoza
Bitandukanye nuburyo bwimiti gakondo ya molekile ntoya hamwe nibiyobyabwenge bya antibody, imiti ya acide nucleic irashobora kwagura imiti kugeza kurwego rwa geneti mbere ya poroteyine.Birateganijwe ko hamwe nogukomeza kwaguka kwerekanwa no gukomeza kunoza uburyo bwo gutanga no guhindura, imiti ya acide nucleique izamenyekanisha abarwayi benshi kandi bahinduke ikindi cyiciro cyibicuruzwa biturika nyuma y’imiti mito ya molekile n’imiti ya antibody.
Ibikoresho bifatika:
1.http: //xueshu.baidu.com/usercenter/paper/show? Paperid = e28268d4b63ddb3b22270ea1763b2892 & site = xueshu_se
2.https: //www.biospace.com/article/isohora
3. Liu Xi, Sun Fang, Tao Qichang;Ubwenge Umwigisha.“Isesengura ry’imiti ya nucleic aside”
4. CICC: ibiyobyabwenge bya acide nucleic, igihe kirageze
Ibicuruzwa bifitanye isano:
Inyama zinyamanswa Direct PCR kit
Igihe cyo kohereza: Nzeri-24-2021
