Isi mmalite: Medical Micro
Mgbe ntiwapụ nke COVID-19 gasịrị, a kwadoro ọgwụ mgbochi mRNA abụọ ngwa ngwa maka ịre ahịa, nke dọtara mmasị karịa na mmepe nke ọgwụ nucleic acid.N'afọ ndị na-adịbeghị anya, ọtụtụ ọgwụ nucleic acid bụ́ ndị nwere ike ịghọ ọgwụ mgbochi ebipụtawo data ụlọ ọgwụ, na-ekpuchi ọrịa obi na ọrịa metabolic, ọrịa imeju, na ọrịa dị iche iche na-adịghị ahụkebe.A na-atụ anya ọgwụ nucleic acid ga-abụ obere ọgwụ molekul na-esote ya na ọgwụ mgbochi mmadụ.Ụdị ọgwụ nke atọ kachasị ukwuu.
Ụdị ọgwụ nucleic acid
Nucleic acid bụ ogige macromolecular dị ndụ nke emere site na polymerization nke ọtụtụ nucleotides, ma bụrụ otu n'ime ihe ndị bụ isi na ndụ.Nucleic acid ọgwụ dị iche iche nke oligoribonucleotides (RNA) ma ọ bụ oligodeoxyribonucleotides (DNA) nwere ọrụ dị iche iche, nke nwere ike na-eme ozugbo na ọrịa na-akpata lekwasịrị mkpụrụ ndụ ihe nketa ma ọ bụ lekwasịrị mRNAs iji na-agwọ ọrịa na gene larịị Ọrụ nke.
▲ Usoro njikọ sitere na DNA gaa na RNA gaa na protein (isi iyi: bing)
Ka ọ dị ugbu a, ọgwụ nucleic acid bụ isi gụnyere antisense nucleic acid (ASO), obere RNA (siRNA), microRNA (miRNA), obere RNA (saRNA), onye ozi RNA (mRNA), aptamer, na ribozyme., Antibody nucleic acid conjugated drugs (ARC), wdg.
Na mgbakwunye na mRNA, nyocha na mmepe nke ọgwụ nucleic acid ndị ọzọ enwetawokwa nlebara anya karịa n'afọ ndị na-adịbeghị anya.N'afọ 2018, a kwadoro ọgwụ siRNA mbụ n'ụwa (Patisiran), na ọ bụ ọgwụ nucleic acid mbụ jiri usoro nnyefe LNP.N'afọ ndị na-adịbeghị anya, ahịa ọgwụ nucleic acid abawanyela ngwa ngwa.Na 2018-2020 naanị, enwere ọgwụ siRNA 4, akwadoro ọgwụ ASO atọ (FDA na EMA).Na mgbakwunye, Aptamer, miRNA na mpaghara ndị ọzọ nwekwara ọtụtụ ọgwụ na ọkwa ụlọ ọgwụ.
Uru na ihe ịma aka nke ọgwụ nucleic acid
Kemgbe 1980s, nyocha na mmepe nke ọgwụ ọhụrụ dabere na ebumnuche ejirila nke nta nke nta gbasaa, ma achọpụtala ọtụtụ ọgwụ ọhụrụ;ọgwụ kemịkalụ obere molecule ọdịnala na ọgwụ mgbochi mmadụ na-arụkọ ọrụ ọgwụ site na ijikọ na-echekwa protein.Ndị na-edozi ahụ nwere ike ịbụ enzymes, ndị na-anabata ya, ọwa ion, wdg.
Ọ bụ ezie na ọgwụ obere molecule nwere uru nke mmepụta dị mfe, nchịkwa ọnụ, ihe ndị na-emepụta ọgwụ na-eme ka mma, na ụzọ dị mfe site na cell membranes, mmepe ha na-emetụta site na ọgwụ ọjọọ nke ihe mgbaru ọsọ (na ma protein ezubere iche nwere nhazi akpa na nha kwesịrị ekwesị)., Omimi, polarity, wdg);dị ka otu isiokwu na Nature2018 si kwuo, naanị 3,000 nke ~ 20,000 protein nke genome mmadụ debere nwere ike ịbụ ọgwụ, na naanị 700 nwere ọgwụ ndị kwekọrọ na ya mepụtara (na tumadi obere kemịkalụ molecule).
Nnukwu uru nke ọgwụ nucleic acid bụ na enwere ike ịmepụta ọgwụ dị iche iche naanị site n'ịgbanwe usoro ntọala nke nucleic acid.E jiri ya tụnyere ọgwụ ndị na-arụ ọrụ na ọkwa protein omenala, usoro mmepe ya dị mfe, rụọ ọrụ nke ọma, na usoro ndu;ma e jiri ya tụnyere ọgwụgwọ DNA nke genomic, ọgwụ nucleic acid enweghị ihe ize ndụ nke njikọta mkpụrụ ndụ ihe nketa ma na-agbanwe agbanwe n'oge ọgwụgwọ.Enwere ike ịkwụsị ọgwụ ahụ mgbe ọgwụgwọ adịghị mkpa.
Ọgwụ Nucleic acid nwere uru doro anya dị ka nkọwa dị elu, arụmọrụ dị elu na mmetụta dị ogologo oge.Agbanyeghị, n'ọtụtụ uru yana mmepe ngwa ngwa, ọgwụ nucleic acid na-echekwa ihe ịma aka dị iche iche ihu.
Otu bụ mgbanwe RNA iji kwalite nkwụsi ike nke ọgwụ nucleic acid yana ibelata immunogenicity.
Nke abụọ bụ mmepe nke ndị na-ebu ibu iji hụ na nkwụsi ike nke RNA n'oge usoro nnyefe nucleic acid na ọgwụ nucleic acid iji ruo mkpụrụ ndụ ebu n'obi / akụkụ akụkụ;
Nke atọ bụ mmelite nke usoro nnyefe ọgwụ.Otu esi emeziwanye usoro nnyefe ọgwụ iji nweta otu mmetụta ahụ na obere doses.
Mgbanwe kemịkalụ nke ọgwụ nucleic acid
Ọgwụ nucleic acid dịpụrụ adịpụ kwesịrị imeri ọtụtụ ihe mgbochi iji banye n'ime ahụ iji rụọ ọrụ.Ihe mgbochi ndị a ebutewokwa ihe isi ike na mmepụta ọgwụ nucleic acid.Otú ọ dị, site na mmepe nke nkà na ụzụ ọhụrụ, ụfọdụ n'ime nsogbu ndị a edoziworị site na mgbanwe kemịkalụ.Na ọganihu na teknụzụ usoro nnyefe ekerewo òkè dị mkpa n'imepụta ọgwụ nucleic acid.
Mgbanwe kemịkalụ nwere ike ịkwalite ikike ọgwụ RNA iguzogide mbibi site na endogenous endonucleases and exonucleases, ma kwalite nrụpụta ọgwụ ike nke ukwuu.Maka ọgwụ siRNA, mgbanwe kemịkalụ nwekwara ike welie nhọrọ nke eriri antisense ha iji belata ọrụ RNAi na-echeghị ya, ma gbanwee akụrụngwa anụ ahụ na kemịkal iji welie ike nnyefe.
1. Chemical mgbanwe nke shuga
N'oge mmalite nke mmepe ọgwụ nucleic acid, ọtụtụ ogige nucleic acid gosipụtara ezigbo ọrụ ndu na vitro, mana ọrụ ha na vivo belatara nke ukwuu ma ọ bụ tụfuru kpamkpam.Isi ihe kpatara ya bụ na enzymes ma ọ bụ ihe ndị ọzọ dị n'ime ahụ na-agbaji ngwa ngwa nucleic acids na-adịghị agbanwe agbanwe.Mgbanwe kemịkalụ nke shuga na-agụnye ngbanwe nke 2-ọnọdụ hydroxyl (2'OH) nke shuga ka methoxy (2'OMe), fluorine (F) ma ọ bụ (2'MOE).Mgbanwe ndị a nwere ike ịbawanye ọrụ na nhọrọ nke ọma, belata mmetụta ndị a na-atụghị anya ya, ma belata mmetụta.
▲Mgbanwe nke shuga (isi mmalite foto: ntụaka 4)
2. Mgbanwe ọkpụkpụ phosphoric acid
Mgbanwe kemịkalụ a na-ejikarị eme ihe nke ọkpụkpụ azụ phosphate bụ phosphorothioate, ya bụ, ikuku oxygen na-adịghị ejikọta na azụ phosphate nke nucleotide na-eji sọlfọ (PS mgbanwe).Mgbanwe PS nwere ike iguzogide mmebi nke nucleases ma welie mmekọrịta nke ọgwụ nucleic acid na protein plasma.Ikike njide, belata ọnụego mkpochapụ gbasara akụrụ ma mụbaa ọkara ndụ.
▲ Mgbanwe nke phosphorothioate (isi mmalite foto: ntụaka 4)
Ọ bụ ezie na PS nwere ike ibelata njikọ nke nucleic acids na mkpụrụ ndụ ihe ezubere iche, mgbanwe PS bụ hydrophobic na kwụsiri ike, yabụ ọ ka bụ mgbanwe dị mkpa na itinye aka na obere acid nucleic na antisense nucleic acid.
3. Mgbanwe nke mgbanaka nke nwere akụkụ ise nke ribose
Mgbanwe nke mgbanaka ribose nke nwere akụkụ ise ka a na-akpọ mgbanwe kemịkalụ nke ọgbọ nke atọ, gụnyere bridged nucleic acid-locked nucleic acid BNAs, peptide nucleic acid PNA, phosphorodiamide morpholino oligonucleotide PMO, mgbanwe ndị a nwere ike ịkwalite ọgwụ acid nucleic Nguzogide nucleases na ihe ndị ọzọ na-emeziwanye ihe.
4. Mgbanwe kemịkalụ ndị ọzọ
Na nzaghachi na mkpa dị iche iche nke ọgwụ nucleic acid, ndị nchọpụta na-emekarị mgbanwe na mgbanwe na ntọala na nucleotide chains iji mee ka nkwụsi ike nke ọgwụ nucleic acid dịkwuo elu.
Ka ọ dị ugbu a, ọgwụ niile na-ezubere iche RNA nke FDA kwadoro bụ RNA analogs ejiri kemịkal mebere, na-akwado ike mgbanwe kemịkalụ.Oligonucleotides nke nwere otu eriri maka ụdị mgbanwe kemịkalụ dị iche iche dị iche iche naanị n'usoro, mana ha niile nwere ihe anụ ahụ na kemịkalụ yiri ya, yabụ nwere ọgwụ pharmacokinetics na ihe ndị dị ndụ.
Nnyefe na nchịkwa nke ọgwụ nucleic acid
Ọgwụ Nucleic acid nke na-adabere naanị na mgbanwe kemịkalụ ka na-agbada ngwa ngwa na mgbasa ọbara, ọ naghị adị mfe ịgbakọ n'ime anụ ahụ e lekwasịrị anya, ọ dịghịkwa adị mfe ịbanye n'ime akpụkpọ ahụ sel e lekwasịrị anya iji ruo ebe a na-eme ihe na cytoplasm.Ya mere, ike nke usoro nnyefe dị mkpa.
Ka ọ dị ugbu a, a na-ekewa vectors ọgwụ nucleic acid ka ọ bụrụ vectors nke nje na-abụghị nke nje.Nke mbụ gụnyere adenovirus-associated virus (AAV), lentivirus, adenovirus na retrovirus, wdg. Ndị ahụ gụnyere ndị na-ebu lipid, vesicles na ihe ndị yiri ya.Site n'echiche nke ọgwụ a na-ere ahịa, vectors viral na ndị na-ebu lipid tozuru oke na nnyefe ọgwụ mRNA, ebe obere ọgwụ nucleic acid na-eji ọtụtụ ndị na-ebu ma ọ bụ nyiwe teknụzụ dị ka liposomes ma ọ bụ GalNAc.
Ka ọ dị ugbu a, a na-enye ọtụtụ ọgwụgwọ nucleotide, gụnyere ihe fọrọ nke nta ka ọ bụrụ ọgwụ nucleic acid niile a kwadoro, na mpaghara, dị ka anya, ọkpụkpụ azụ, na imeju.Nucleotides na-abụkarị nnukwu polyanions hydrophilic, ihe onwunwe a pụtara na ha enweghị ike ịgafe n'ụzọ dị mfe site na akpụkpọ ahụ plasma.N'otu oge ahụ, ọgwụ ọgwụgwọ oligonucleotide na-emekarị enweghị ike ịgafe ihe mgbochi ụbụrụ ọbara (BBB), ya mere nnyefe na usoro nhụjuanya nke etiti (CNS) bụ ihe ịma aka na-esote maka ọgwụ nucleic acid.
Okwesiri iburu n'uche na nhazi usoro nucleic acid na ngbanwe nucleic acid bu ihe nlebara anya nke ndi nyocha n'ugbo.N'ihi na chemical mgbanwe, chemically gbanwetụrụ nucleic acid, na-abụghị eke nucleic acid usoro imewe ma ọ bụ mma, nucleic acid mejupụtara, vector ewu, nucleic acid usoro njikọ, wdg Nka na-achị bụ n'ozuzu patentable ngwa isiokwu.
Were coronavirus ọhụrụ dịka ọmụmaatụ.Ebe ọ bụ na RNA ya bụ ihe dị n'ụdị okike na okike, "RNA nke coronavirus ọhụrụ" n'onwe ya enweghị ike ịnye patent.Agbanyeghị, ọ bụrụ na onye nyocha sayensị kewapụ ma ọ bụ wepụta RNA ma ọ bụ iberibe nke teknụzụ amabeghị na teknụzụ sitere na coronavirus ọhụrụ na nke mbụ wee tinye ya (dịka ọmụmaatụ, gbanwee ya ka ọ bụrụ ọgwụ mgbochi), mgbe ahụ enwere ike inye ma nucleic acid na ọgwụ mgbochi ahụ ikike ikike ikike dịka iwu siri dị.Na mgbakwunye, ụmụ irighiri ihe nucleic acid arụpụtara na nyocha nke coronavirus ọhụrụ, dị ka primers, probes, sgRNA, vectors, wdg, bụ ihe niile nwere ikike.
Okwu mmechi
N'adịghị ka usoro ọgwụ ọgwụ kemịkalụ obere molekul ọdịnala na ọgwụ mgbochi mmadụ, ọgwụ nucleic acid nwere ike ịgbatị nchọpụta ọgwụ ruo ogo mkpụrụ ndụ ihe nketa tupu protein.A na-ahụ anya na site na mmụba na-aga n'ihu nke ihe ngosi yana mmụba na-aga n'ihu nke nnyefe na teknụzụ mgbanwe, ọgwụ nucleic acid ga-eme ka ndị ọrịa dịkwuo ukwuu ma bụrụ n'ezie klas ọzọ nke ngwaahịa mgbawa mgbe obere ọgwụ kemịkal molecule na ọgwụ mgbochi.
Ihe nrụtụ aka:
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;Nna-ukwu amamihe."Nnyocha nke patentability nke ọgwụ nucleic acid"
4. CICC: ọgwụ nucleic acid, oge eruola
Ngwaahịa ndị emetụtara:
Ngwa anụ ahụ Animal Direct PCR
Oge nzipu: Sep-24-2021
