Xigasho: Medical Micro

Ka dib markii uu dillaacay COVID-19, laba tallaal oo mRNA ah ayaa si dhakhso ah loogu oggolaaday suuqgeyn, taas oo soo jiidatay fiiro gaar ah horumarinta daawooyinka nucleic acid.Sanadihii la soo dhaafay, tiro ka mid ah daawooyinka nucleic acid kuwaas oo awood u leh inay noqdaan dawooyinka xannibaadda ayaa daabacay xogta bukaan-socodka, oo daboolaya cudurrada wadnaha iyo dheef-shiid kiimikaadka, cudurrada beerka, iyo cudurro kala duwan oo dhif ah.Daawooyinka aashitada nukliyeerka ayaa la filayaa inay noqdaan dawooyinka molecule yar yar ee soo socda iyo dawooyinka lidka ku ah jidhka.Nooca saddexaad ee ugu weyn ee daroogada.

Qaybta daawada nukleic acid

Nucleic acid waa unug makromolecular bayooloji ah oo ay samaysay polymerization ee nucleotide badan, waana mid ka mid ah walxaha aasaasiga ah ee nolosha.Daawooyinka Nucleic acid waa noocyo kala duwan oo oligoribonucleotides (RNA) ama oligodeoxyribonucleotides (DNA) oo leh hawlo kala duwan, kuwaas oo si toos ah ugu dhaqmi kara cudurada keena hiddaha bartilmaameedka ama bartilmaameedka mRNA-yada si loogu daaweeyo cudurrada heerka hidda-wadaha Doorka.

▲ Habka isku dhafka DNA ilaa RNA ilaa borotiinka (Isha sawirka: Bing)

Waqtigan xaadirka ah, daawooyinka nucleic acid ee ugu muhiimsan waxaa ka mid ah antisense nucleic acid (ASO), RNA (siRNA), microRNA (miRNA), RNA yar oo firfircoon (saRNA), Messenger RNA (mRNA), aptamer, iyo ribozyme., Daawooyinka isku dhafka ah ee nucleic acid (ARC), iwm.

Marka lagu daro mRNA, cilmi baarista iyo horumarinta daawooyinka kale ee nucleic acid ayaa sidoo kale helay fiiro gaar ah sannadihii la soo dhaafay.Sannadkii 2018, daawadii siRNA ee ugu horreysay adduunka (Patisiran) ayaa la ansixiyay, waxayna ahayd daawadii ugu horreysay ee nucleic acid si ay u isticmaasho nidaamka gaarsiinta LNP.Sanadihii la soo dhaafay, xawaaraha suuqa ee dawooyinka aashitada nukliyeerka ayaa sidoo kale kor u kacay.2018-2020 oo keliya, waxaa jira 4 dawooyin siRNA ah, Saddex daawo oo ASO ah ayaa la ansixiyay (FDA iyo EMA).Intaa waxaa dheer, Aptamer, miRNA iyo goobo kale ayaa sidoo kale leh daawooyin badan oo ku jira marxaladda bukaan-socodka.

Faa'iidooyinka iyo caqabadaha daawooyinka nucleic acid

Tan iyo 1980-meeyadii, cilmi-baarista iyo horumarinta dawooyinka cusub ee bartilmaameedka ku salaysan ayaa si tartiib tartiib ah u ballaartay, waxaana la helay tiro badan oo daawooyin cusub ah;Daawooyinka kiimikaad yar-yar ee dhaqameed iyo daawooyinka antibody-ka labaduba waxay sameeyaan saameyn farmaajo iyagoo ku xiraya bartilmaameedka borotiinka.Borotiinnada la beegsanayo waxay noqon karaan Enzymes, reseptors, channels ion, iwm.

Inkasta oo daawooyinka yaryar-molecule ay leeyihiin faa'iidooyinka wax-soo-saarka fudud, maamulka afka, sifooyinka farmashiyaha ee ka fiican, iyo marin sahlan oo loo maro xuubka unugyada, korriinkooda ayaa saameeya daroogada bartilmaameedka (iyo haddii borotiinka bartilmaameedku leeyahay qaab-dhismeedka jeebka iyo cabbirka ku habboon)., Qoto dheer, polarity, iwm.);Sida ku cad maqaal ku jira Nature2018, kaliya 3,000 ee ~ 20,000 borotiinada ah ee lagu dhejiyay genome-ka aadanaha ayaa noqon kara dawooyin, kaliya 700 oo keliya ayaa leh dawooyin u dhigma oo la sameeyay (U badan kiimikooyinka molecule yar yar).

Faa'iidada ugu weyn ee dawooyinka nucleic acid waa in dawooyin kala duwan lagu soo saari karo oo keliya iyadoo la beddelo nidaamka asaasiga ah ee nucleic acid.Marka la barbardhigo daroogooyinka ka shaqeeya heerka borotiinka dhaqameed, geeddi-socodkeeda kobcintu waa mid sahlan, hufan, iyo bayooloji gaar ah;marka la barbar dhigo daawaynta heerka DNA-ga genomic, daawooyinka nucleic acid ma laha khatar isdhexgalka hidda-wadaha oo aad bay u dabacsan yihiin wakhtiga daawaynta.Daawada waa la joojin karaa marka aan daawayn loo baahnayn.

Daawooyinka Nucleic acid waxay leeyihiin faa'iidooyin muuqda sida qeexid sare, waxtar sare iyo saameyn waqti dheer ah.Si kastaba ha ahaatee, iyada oo leh faa'iidooyin badan iyo horumarinta la dedejiyey, daawooyinka nucleic acid waxay sidoo kale wajahayaan caqabado kala duwan.

Mid waa wax ka beddelka RNA si kor loogu qaado xasilloonida daawooyinka nucleic acid oo loo yareeyo difaaca jirka.

Midda labaad waa horumarinta sidayaal si loo hubiyo xasilloonida RNA inta lagu jiro habka wareejinta aashitada nucleic iyo daawooyinka nucleic acid si ay u gaaraan unugyada bartilmaameedka / xubnaha bartilmaameedka;

Midda saddexaad waa hagaajinta habka gudbinta daroogada.Sida loo hagaajiyo habka bixinta daroogada si loo gaaro saameyn isku mid ah oo leh qiyaaso hooseeya.

Wax ka beddel kiimikaad ee daawooyinka nucleic acid

Daawooyinka nucleic acid-ka ee ka baxsan waxay u baahan yihiin inay ka gudbaan caqabado badan si ay u galaan jirka si ay door uga ciyaaraan.Caqabadahan ayaa sidoo kale sababay dhibaatooyin xagga horumarinta daawooyinka nucleic acid.Si kastaba ha noqotee, horumarinta tignoolajiyada cusub, dhibaatooyinka qaar ayaa mar hore lagu xalliyay wax ka beddelka kiimikada.Horumarka tignoolajiyada habka dhalmada ayaa door muhiim ah ka ciyaartay horumarinta daawooyinka nucleic acid.

Wax ka beddelka kiimikadu waxay kor u qaadi kartaa awoodda daawooyinka RNA si ay uga hortagaan hoos u dhaca by endogenous endonucleases iyo exonucleases, waxayna si weyn u wanaajisaa waxtarka daawooyinka.Daawooyinka siRNA, wax ka beddelka kiimikaad waxa kale oo ay wanaajin kartaa xulashada xargaha dareenkooda lidka ku ah si loo yareeyo dhaqdhaqaaqa RNAi ee ka baxsan, oo ay u beddelaan sifooyinka jidhka iyo kiimikaad si kor loogu qaado awoodaha dhalmada.

1. Wax ka beddel kiimikaad ee sonkorta

Marxaladda hore ee horumarinta daroogada nucleic acid, xeryahooda nucleic acid badan ayaa soo bandhigay firfircoonida bayooloji ee wanaagsan ee vitro, laakiin dhaqdhaqaaqooda vivo ayaa si weyn loo dhimay ama gebi ahaanba lumay.Sababta ugu weyn ayaa ah in asiidhyada nucleic-ka ah ee aan la beddelin ay si fudud u burburiyaan enzymes ama walxaha kale ee jirka ku jira.Wax ka beddelka kiimikaad ee sonkorta inta badan waxa ka mid ah wax ka beddelka 2-boos hydroxyl (2'OH) ee sonkorta oo loo beddelo methoxy (2'OMe), fluorine (F) ama (2'MOE).Wax-ka-beddeladani waxay si guul leh u kordhin karaan dhaqdhaqaaqa iyo xulashada, yareeyaan saamaynta bartilmaameedka, iyo yaraynta waxyeellooyinka.

v Wax ka beddel kiimikaad ee sonkorta ( isha sawirka: tixraac 4)

2. Wax ka beddelka lafaha fosfooraska

Wax ka beddelka kiimikaad ee inta badan la isticmaalo ee laf-dhabarka fosfooraska waa phosphorothioate, taas oo ah, ogsijiin aan isku xidhnayn ee laf-dhabarka fosfate ee nucleotide ayaa lagu beddelaa baaruud (PS modification).Wax ka beddelka PS wuxuu u adkeysan karaa hoos u dhaca nukleases wuxuuna wanaajin karaa isdhexgalka daawooyinka nucleic acid iyo borotiinnada balaasmaha.Awoodda isku-xidhka, yaraynta heerka nadiifinta kelyaha oo kordhiya nolosha badhkeed.

v Beddelka fosfoortiyoate (Isha sawirka: tixraac 4)

Inkasta oo PS laga yaabo inay hoos u dhigto xidhiidhka nucleic acids iyo hiddo-wadaha bartilmaameedka ah, wax ka beddelka PS waa hydrophobic iyo xasilloon, sidaas darteed weli waa isbeddel muhiim ah oo lagu faragelinayo asiidhyada nucleic yar yar iyo asiidhyada nucleic-ka lidka ku ah.

3. Wax ka beddelka giraanta shanta xubnood ee ribose

Wax ka beddelka giraanta shanta xubnood ee ribose waxaa loo yaqaanaa isbeddelka kiimikaad ee jiilka saddexaad, oo ay ku jiraan nucleic acid-quful nucleic acid BNAs, peptide nucleic acid PNA, phosphorodiamide morpholino oligonucleotide PMO, isbeddelladani waxay sii kordhin karaan daawooyinka nucleic acid Resistance to nucleases, iwm.

4. Wax ka beddel kiimikaad oo kale

Iyadoo laga jawaabayo baahiyaha kala duwan ee daawooyinka nucleic acid, cilmi-baarayaashu waxay badanaa sameeyaan isbeddel iyo isbeddel ku yimaada saldhigyada iyo silsiladaha nucleotide si loo kordhiyo xasilloonida daawooyinka nucleic acid.

Ilaa hadda, dhammaan dawooyinka bartilmaameedka RNA ee ay ansixisay FDA waa kuwa kiimiko ahaan loo farsameeyay RNA analogs, oo taageeraya isticmaalka wax ka beddelka kiimikaad.Oligonucleotides-ka-hal-xidhan ee qaybaha wax-ka-beddelka kiimikaad ee gaarka ah waxay ku kala duwan yihiin oo keliya isku xigxiga, laakiin dhammaantood waxay leeyihiin sifooyin jireed iyo kiimiko oo isku mid ah, sidaas darteedna waxay leeyihiin farmashiisteyaal caadi ah iyo hanti bayooloji.

Bixinta iyo maamulka daawooyinka nucleic acid

Daawooyinka aashitada nukliyeerka ah ee ku tiirsan wax ka beddelka kiimikaad oo keliya ayaa weli si fudud u naaqusaya si degdeg ah wareegga dhiigga, ma fududa in ay ku ururaan unugyada bartilmaameedka ah, mana fududa in ay si wax ku ool ah u galaan xuubka unugyada bartilmaameedka si ay u gaaraan goobta ficilka ee cytoplasm.Sidaa darteed, awoodda nidaamka bixinta ayaa loo baahan yahay.

Waqtigan xaadirka ah, xididada daawada nucleic acid waxay inta badan u qaybsan yihiin fayraska iyo kuwa aan fayraska ahayn.Kan hore waxaa ka mid ah fayraska la-xiriira adenovirus (AAV), lentivirus, adenovirus iyo retrovirus, iwm. Kuwaas waxaa ka mid ah sidayaasha dufanka leh, vesicles iyo wixii la mid ah.Marka loo eego dawooyinka la suuq geeyo, fayraska fayrasyada iyo kuwa dufanka qaada ayaa aad ugu bislaaday keenista dawooyinka mRNA, halka dawooyinka aashitada nukliyeerka yar ay isticmaalaan sideyaal badan ama aalado tignoolajiyadeed sida liposomes ama GalNAc.

Ilaa hadda, inta badan daawaynta nucleotide, oo ay ku jiraan ku dhawaad ​​dhammaan daawooyinka nucleic acid ee la ansixiyay, ayaa lagu maamulay gudaha, sida indhaha, xangulada, iyo beerka.Nucleotides inta badan waa polyanions hydrophilic weyn, iyo hantida this ka dhigan tahay in ayan si fudud u dhex mari karin xuubka balasmaha.Isla mar ahaantaana, dawooyinka daaweynta oligonucleotide-ku-saleysan sida caadiga ah kama gudbi karaan xannibaadda maskaxda-maskaxda (BBB), markaa gaarsiinta habka dhexe ee neerfayaasha (CNS) waa caqabadda xigta ee daawooyinka nucleic acid.

Waxaa xusid mudan in naqshadeynta isku xigxiga aashitada nucleic iyo wax ka beddelka aashitada nucleic ay hadda diiradda saaraan cilmi-baarayaasha goobta.Wax ka beddelka kiimikaad, aashitada nucleic-ka ah ee la beddelay, naqshadaynta ama hagaajinta taxanaha nucleic acid, halabuurka aashitada nucleic, dhismaha vector, hababka isku-darka acid nucleic, iwm.

Tusaale ahaan u soo qaado coronavirus-ka cusub.Maadaama RNA ay tahay walax ku jirta qaabka dabiiciga ah ee dabiiciga ah, "RNA ee coronavirus-ka cusub" laftiisa lama siin karo rukhsad.Si kastaba ha noqotee, haddii cilmi-baaraha sayniska uu ka sooco ama ka saaro RNA ama jajab aan lagu aqoon tignoolajiyada coronavirus-ka cusub markii ugu horeysay oo uu isticmaalo (tusaale ahaan, u beddelo tallaal), markaa labadaba nucleic acid iyo tallaalka ayaa la siin karaa xuquuqaha patent si waafaqsan sharciga.Intaa waxaa dheer, unugyaraha aashitada nucleic-ka ah ee si macmal ah loo farsameeyay ee cilmi baarista coronavirus-ka cusub, sida primers, probes, sgRNA, vectors, iwm, dhamaantood waa shay la aqoonsan karo.

Gabagabadii

Si ka duwan habka dawooyinka kiimikada molecule yar yar ee dhaqameed iyo daawooyinka antibody, daawooyinka nucleic acid waxay kordhin karaan helitaanka daroogada ilaa heerka hidda-socodka ka hor borotiinada.Waxaa la saadaalin karaa in iyadoo la sii balaadhinayo calaamadaha iyo hagaajinta joogtada ah ee tignoolajiyada gaarsiinta iyo wax ka beddelka, daawooyinka nucleic acid waxay faafin doonaan bukaanno badan oo cudur ah oo run ahaantii noqon doona nooc kale oo walxaha qarxa ah ka dib dawooyinka kiimikada molecule yar iyo dawooyinka ka hortagga.

Qalabka tixraaca:

1.http://xueshu.baidu.com/uscenter/paper/show?paperid=e28268d4b63ddb3b22270ea1763b2892&site=xueshu_se

2.https://www.biospace.com/article/releases/wave-life-sciences-announces-initiation-of-dosing-in-phase-1b-2a-focus-c9-clinical-trial-of-wve- 004-in-amyotrophic-lateral-sclerosis-and-frontotempo

3. Liu Xi, Sun Fang, Tao Qichang;Xikmad Macalin."Falanqaynta patentability ee daawooyinka nucleic acid"

4. CICC: Daawooyinka aashitada nukliyeerka, wakhtigu wuu yimid

Alaabooyinka La Xiriira:

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