Punavai: Medical Micro
Ina ua maeʻa le faʻamaʻi o le COVID-19, e lua tui mRNA na vave faʻamaonia mo le maketiina, lea na tosina atu ai le tele o le mafaufau i le atinaʻeina o vailaʻau nucleic acid.I tausaga talu ai nei, o le tele o vailaʻau nucleic acid o loʻo i ai le gafatia e avea ma vailaʻau blockbuster ua faʻasalalau faʻamaumauga o falemaʻi, e aofia ai faʻamaʻi fatu ma gasegase, faʻamaʻi ate, ma faʻamaʻi eseese e le masani ai.O vaila'au o le nucleic acid e fa'amoemoe e avea ma isi vaila'au mole laiti ma vaila'au fa'ama'i.Le ituaiga lona tolu o fualaau faasaina.
Nucleic acid vaega o fualaau
Nucleic acid o se meaola macromolecular faʻapipiʻiina e ala i le polymerization o le tele o nucleotides, ma o se tasi o mea sili ona taua o le olaga.Nucleic acid vailaʻau o se ituaiga o oligoribonucleotides (RNA) poʻo le oligodeoxyribonucleotides (DNA) faʻatasi ai ma galuega eseese, e mafai ona galue saʻo i faʻamaʻi faʻamaʻi faʻamaʻi faʻamaʻi poʻo mRNA taulaʻi e togafitia faʻamaʻi i le gene level Le matafaioi a.
▲O le faʻasologa o le faʻasologa mai le DNA i le RNA i le polotini (Amataga ata: bing)
I le taimi nei, o vailaʻau autu o le nucleic acid e aofia ai le antisense nucleic acid (ASO), RNA faʻalavelave laiti (siRNA), microRNA (miRNA), RNA faʻagaoioia laiti (saRNA), avefeʻau RNA (mRNA), aptamer, ma ribozyme., Antibody nucleic acid conjugated drugs (ARC), ma isi.
I le faaopoopo atu i le mRNA, o le suʻesuʻega ma le atinaʻeina o isi vailaʻau nucleic acid ua sili atu le gauai i tausaga talu ai nei.I le 2018, na faʻamaonia ai le siRNA muamua o le siRNA (Patisiran), ma o le vailaʻau muamua o le nucleic acid na faʻaaogaina le LNP delivery system.I tausaga talu ai nei, ua faʻavaveina foi le saoasaoa o maketi o vailaʻau nucleic acid.I le 2018-2020 lava ia, e 4 siRNA vailaʻau, Tolu ASO vailaʻau na faʻamaonia (FDA ma EMA).E le gata i lea, o Aptamer, miRNA ma isi matāʻupu e iai foʻi le tele o vailaʻau i le falemaʻi.
Tulaga lelei ma lu'itau o vaila'au nucleic acid
Talu mai le 1980s, o le suʻesuʻega ma le atinaʻeina o vailaʻau fou e faʻatatau i faʻamoemoega ua faasolosolo malie ona faʻalauteleina, ma ua maua le tele o vailaʻau fou;o vaila'au vaila'au mole mole laiti masani ma vaila'au fa'aantibody e fa'atino uma a'afiaga fa'afoma'i e ala i le fusifusia i polotini fa'atatau.O polotini taulaʻi e mafai ona avea ma Enzymes, tali, ion channels, ma isi.
E ui lava o vailaʻau laiti-moli e iai le lelei o le faʻaogaina faigofie, faʻaogaina tautala, mea e sili atu le pharmacokinetic, ma le faigofie ona alu i totonu o sela sela, o lo latou atinaʻe e aʻafia i le faʻaogaina o vailaʻau o le sini (ma pe o le porotini sini e iai le fausaga talafeagai ma le lapoa)., loloto, polarity, ma isi);e tusa ai ma se tusiga i le Nature2018, naʻo le 3,000 o le ~ 20,000 polotini faʻapipiʻiina e le genome o le tagata e mafai ona avea ma vailaʻau, ma e naʻo le 700 na faʻatupuina fualaau faʻatatau (i le tele o vailaʻau mole laiti).
Ole aoga tele ole nucleic acid ole vaila'au eseese e mafai ona atia'e ile na'o le suia ole fa'asologa o le nucleic acid.Fa'atusatusa i vaila'au o lo'o galue i le tulaga masani o le porotini, o lona fa'agasologa o le atina'e e faigofie, lelei, ma fa'apitoa fa'aolaola;fa'atusatusa i le genomic DNA-level treatment, nucleic acid drugs e leai se lamatiaga o le tu'ufa'atasiga o kenera ma e sili atu ona fetu'una'i i le taimi o togafitiga.E mafai ona taofi le vailaʻau pe a leai se togafitiga e manaʻomia.
O vailaʻau o le nucleic acid e iai faʻamanuiaga manino e pei o le maualuga maualuga, maualuga le lelei ma le umi o le aʻafiaga.Ae ui i lea, faatasi ai ma le tele o mea lelei ma le faʻavaveina o le atinaʻe, o vailaʻau nucleic acid o loʻo feagai foi ma luitau eseese.
O le tasi o le RNA suiga e faʻaleleia ai le mautu o vailaʻau nucleic acid ma faʻaitiitia ai le immunogenicity.
O le lona lua o le atinaʻeina o vaʻavaʻa e faʻamautinoa le mautu o le RNA i le taimi o le faʻafeiloaʻiga o le nucleic acid ma vailaʻau nucleic acid e oʻo atu ai i sela / totoga faʻamoemoe;
O le lona tolu o le faʻaleleia o le faʻaogaina o vailaʻau.Faʻafefea ona faʻaleleia le faiga o le tuʻuina atu o vailaʻau e ausia ai le aafiaga tutusa ma le maualalo o tui.
Suiga vaila'au o vaila'au nucleic acid
Ole vaila'au ole nucleic acid e mana'omia ona foia le tele o fa'alavelave ina ia mafai ona ulufale i totonu o le tino e fai se sao.O nei faʻalavelave ua mafua ai foʻi faigata i le atinaʻeina o vailaʻau nucleic acid.Ae ui i lea, faatasi ai ma le atinaʻeina o tekonolosi fou, o nisi o faʻafitauli ua uma ona foia e ala i suiga o vailaʻau.Ma o le alualu i luma i le tuʻuina atu o tekinolosi faʻaogaina ua faia se sao taua i le atinaʻeina o vailaʻau nucleic acid.
Ole suiga ole vaila'au e mafai ona fa'aleleia ai le malosi ole RNA vaila'au e tete'e atu ai i le fa'aleagaina e le endogenous endonucleases ma exonucleases, ma fa'aleleia atili ai le aoga o vaila'au.Mo vaila'au o le siRNA, e mafai fo'i ona fa'aleleia atili le filifilia o latou manoa e fa'aitiitia ai le gaioiga o le RNAi, ma suia mea fa'aletino ma vaila'au e fa'aleleia ai le mafai ona tu'uina atu.
1. Suiga vaila'au o le suka
I le amataga o le atinaʻeina o vailaʻau nucleic acid, o le tele o vailaʻau nucleic acid na faʻaalia ai le lelei o meaola ola i vitro, ae o la latou gaioiga i vivo na matua faʻaitiitia pe leiloa atoa.O le mafuaaga autu o le le suia o le nucleic acids e faigofie ona talepeina e enzymes poʻo isi mea faʻapitoa i totonu o le tino.Ole suiga ole vaila'au ole suka e aofia ai le suiga ole 2-tulaga hydroxyl (2'OH) ole suka ile methoxy (2'OMe), fluorine (F) po'o le (2'MOE).O nei suiga e mafai ona fa'atuputeleina lelei le gaioiga ma le filifilia, fa'aitiitia a'afiaga i fafo, ma fa'aitiitia a'afiaga.
▲ Suiga kemisi o le suka (puna aʻe: faʻamatalaga 4)
2. Phosphoric acid auivi suiga
O le faʻaaogaina o vailaʻau faʻaaogaina o le phosphate backbone o le phosphorothioate, o lona uiga, o se okesene e le faʻapipiʻiina i le phosphate backbone o le nucleotide ua suia i le sulfur (PS modification).O le suiga o le PS e mafai ona tetee atu i le faʻaleagaina o nucleases ma faʻaleleia le fegalegaleaiga o vailaʻau faʻamaʻi nucleic ma protein plasma.E mafai ona fusifusia, faʻaitiitia le kilia o fatugaʻo ma faʻateleina le afa-ola.
▲Suiga o le phosphorothioate (punavai ata: fa'amatalaga 4)
E ui lava e mafai e le PS ona faʻaitiitia le fesoʻotaʻiga o nucleic acids ma genes taulaʻi, PS suiga e sili atu hydrophobic ma mautu, o lea e avea pea ma suiga taua i le faʻalavelaveina o meaʻai nucleic laiti ma antisense nucleic acids.
3. Suiga o le mama lima itu o le ribose
O le suiga o le mama e lima-membered o le ribose ua taʻua o le tolu-tupulaga suiga kemikolo, e aofia ai bridged nucleic acid-locked nucleic acid BNAs, peptide nucleic acid PNA, phosphorodiamide morpholino oligonucleotide PMO, o nei suiga e mafai ona faʻaleleia atili vailaʻau nucleic acid Resistance to nucleases ma faʻaleleia affinity, ma isi.
4. O isi suiga o vaila'au
I le tali atu i manaʻoga eseese o vailaʻau nucleic acid, e masani ona faia e tagata suʻesuʻe suiga ma suiga i luga o faʻavae ma filifili nucleotide e faʻateleina ai le mautu o vailaʻau nucleic acid.
E oʻo mai i le taimi nei, o vailaʻau uma e faʻatatau i le RNA ua faʻamaonia e le FDA o vailaʻau faʻainisinia RNA analogs, e lagolagoina ai le aoga o suiga vailaʻau.Ole oligonucleotides fa'asolo tasi mo fa'avasegaga fa'avasegaga fa'apitoa e eseese na'o le fa'asologa, ae o lo'o i ai uma lava mea fa'aletino ma vaila'au, ma o lea e masani ai pharmacokinetics ma mea ola.
Tuuina atu ma le faʻaaogaina o vailaʻau nucleic acid
Nucleic acid vailaʻau e faʻalagolago naʻo le suiga o vailaʻau e faigofie lava ona faʻaleagaina vave i le toto, e le faigofie ona faʻaputuina i totonu o masini faʻapipiʻi, ma e le faigofie ona faʻaoga lelei le membrane cell target e oʻo atu i le nofoaga o gaioiga i le cytoplasm.O le mea lea, e manaʻomia le mana o le tuʻuina atu.
I le taimi nei, o vailaʻau vailaʻau nucleic acid e masani ona vaevaeina i viral ma non-viral vectors.O le mea muamua e aofia ai le adenovirus-associated virus (AAV), lentivirus, adenovirus ma retrovirus, ma isi mea e aofia ai lipid carriers, vesicles ma isi mea faapena.Mai le vaʻaiga o vailaʻau faʻatau atu, o vailaʻau viral ma lipid carriers e sili atu ona matua i le tuʻuina atu o vailaʻau mRNA, ae o vailaʻau faʻamaʻi nucleic acid e faʻaogaina ai le tele o faʻasalalauga poʻo faʻatekonolosi e pei o liposomes poʻo GalNAc.
E oo mai i le taimi nei, o le tele o togafitiga o le nucleotide, e aofia ai le toetoe lava o vailaʻau faʻamaonia uma o le nucleic acid, o loʻo faʻatinoina i le lotoifale, e pei o mata, ivi, ma le ate.Nucleotides e masani lava o polyanions hydrophilic lapopoa, ma o lenei meatotino o lona uiga e le faigofie ona latou ui atu i le membrane plasma.I le taimi lava e tasi, o le oligonucleotide-based therapeutic drugs e masani lava e le mafai ona sopoia le pa puipui o le toto-faiai (BBB), o le tuʻuina atu lea i le fatugalemu o le tino (CNS) o le isi luʻitau lea mo vailaʻau nucleic acid.
E taua le maitauina o le faʻasologa o le faʻasologa o le nucleic acid ma le suiga o le nucleic acid o loʻo taulaʻi nei i ai le au suʻesuʻe i le fanua.Mo le suiga o vaila'au, vaila'au nucleic acid ua suia, mamanu fa'asologa o le nucleic acid fa'alenatura po'o le fa'aleleia atili, fa'apipi'iina o le nucleic acid, fau fa'ameamea, auala fa'atutuina o le nucleic acid, ma isi.
Ave le coronavirus fou e fai ma faʻataʻitaʻiga.Talu ai ona o lona RNA o se mea o loʻo i ai i le natura masani i le natura, o le "RNA o le coronavirus fou" lava ia e le mafai ona tuʻuina atu se pateni.Ae peitaʻi, afai o se tagata suʻesuʻe suʻesuʻe faʻasaienisi faʻateʻaina pe aveese le RNA poʻo ni vaega e le o iloa i tekinolosi mai le coronavirus fou mo le taimi muamua ma faʻaaogaina (mo se faʻataʻitaʻiga, suia i se tui), ona mafai lea ona tuʻuina atu uma le nucleic acid ma le tui e tusa ai ma le tulafono.E le gata i lea, o molelaʻau nucleic acid faʻapipiʻiina i suʻesuʻega o le coronavirus fou, e pei o primers, probes, sgRNA, vectors, ma isi, o mea uma e mafai ona pateni.
O saunoaga faaiu
E ese mai le faiga o vailaʻau faʻamaʻi mole laiti masani ma vailaʻau faʻamaʻi, vailaʻau nucleic acid e mafai ona faʻalauteleina le suʻesuʻeina o vailaʻau i le tulaga faʻavae aʻo leʻi faia polotini.O loʻo vaʻaia o le faʻaauau pea o faʻamatalaga ma le faʻaauau pea o le faʻaleleia o le tuʻuina atu ma le faʻaleleia o tekonolosi, o vailaʻau o le nucleic acid o le a faʻateleina le tele o tagata mamaʻi ma avea moni ma se isi vasega o mea pāpā pe a maeʻa vailaʻau vailaʻau mole mole ma vailaʻau antibody.
Fa'asinomaga:
1.http://xueshu.baidu.com/usercenter/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-frontotemporal-dementia/
3. Liu Xi, Sun Fang, Tao Qichang;Matai Poto.“Suʻesuʻega o le patentability o vailaʻau nucleic acid”
4. CICC: nucleic acid drugs, ua oo mai le taimi
Oloa Fa'atatau:
Taimi meli: Sep-24-2021
