Site na mmepe teknụzụ na-aga n'ihu na teknụzụ ihe omimi, mmekọrịta dị n'etiti mmụgharị mkpụrụ ndụ ihe nketa na ntụpọ na ọrịa enwetala nghọta miri emi karị.Nucleic acid adọtala nlebara anya nke ukwuu n'ihi nnukwu ikike ha nwere itinye n'ọrụ na nyocha na ọgwụgwọ ọrịa.Ọgwụ nucleic acid na-ezo aka na mpempe DNA ma ọ bụ RNA arụpụtara n'onwe ya nwere ọrụ ọgwụgwọ ọrịa.Ọgwụ ndị dị otú ahụ nwere ike ime ozugbo na mkpụrụ ndụ ihe nketa na-ebute ọrịa ma ọ bụ ọrịa na-ebute mRNA, ma na-ekere òkè n'ịgwọ ọrịa na ọkwa nke mkpụrụ ndụ ihe nketa.E jiri ya tụnyere obere ọgwụ molekul ọdịnala na ọgwụ mgbochi mmadụ, ọgwụ nucleic acid nwere ike ịhazi ngosipụta nke mkpụrụ ndụ ihe nketa na-akpata ọrịa sitere na mgbọrọgwụ, ma nwee njirimara nke "ịgwọ mgbaàmà na ịgwọ ihe kpatara ya".Nucleic acid ọgwụ nwekwara uru doro anya dị ka arụmọrụ dị elu, obere nsi, na nnukwu nkọwapụta.Ebe ọ bụ na ewepụtara ọgwụ fomivirsen sodium nke mbụ nucleic acid na 1998, a kwadoro ọtụtụ ọgwụ nucleic acid maka ọgwụgwọ ụlọ ọgwụ.

Ọgwụ nucleic acid dị ugbu a n'ahịa n'ụwa niile gụnyere antisense nucleic acid (ASO), obere RNA (siRNA) na-etinye aka na nucleic acid aptamers.Ewezuga nucleic acid aptamers (nke nwere ike gafere 30 nucleotides), ọgwụ nucleic acid na-abụkarị oligonucleotides nke mejupụtara 12 ruo 30 nucleotides, nke a makwaara dị ka ọgwụ oligonucleotide.Na mgbakwunye, miRNA, ribozymes na deoxyribozymes egosiwokwa nnukwu uru mmepe na ọgwụgwọ ọrịa dị iche iche.Nucleic acid ọgwụ aghọwo otu n'ime ndị kasị ekwe nkwa ubi na nyocha na mmepe nke biomedicine taa.

Ọmụmaatụ nke ọgwụ nucleic acid akwadoro

Antisense nucleic acid

Teknụzụ Antisense bụ teknụzụ mmepe ọgwụ ọhụrụ dabere na ụkpụrụ Watson-Crick base complementation, na-eji DNA ma ọ bụ iberibe RNA arụkọ ọrụ nke organism mebere ma ọ bụ mebere ya ka ọ hazie nkọwapụta mkpụrụ ndụ ihe nketa.Nucleic acid antisense nwere usoro ntọala dabara na RNA ebumnuche ma nwee ike jikọta ya na ya.Acid nucleic nke antisense n'ozuzu gụnyere DNA antisense, antisense RNA na ribozymes.N'ime ha, n'ihi njirimara nke nkwụsi ike dị elu na ọnụ ala dị ala nke DNA antisense, DNA antisense nọ n'ọnọdụ kachasị na nyocha na ntinye nke ọgwụ antisense nucleic acid ugbu a.

Fomivirsen sodium (aha ahia Vitravene) bụ Ionis Novartis mepụtara.N'August 1998, FDA kwadoro ya maka ọgwụgwọ cytomegalovirus retinitis na ndị ọrịa immunocompromised (karịsịa ndị ọrịa AIDS), na-aghọ ọgwụ nucleic acid mbụ a ga-ere ahịa.Fomivirsen na-egbochi nkwupụta protein akụkụ akụkụ nke CMV site na ijikọta mRNA (IE2) kpọmkwem, si otú a na-achịkwa okwu nke mkpụrụ ndụ ihe nketa viral iji nweta mmetụta ọgwụgwọ.Otú ọ dị, n'ihi mpụta nke ọgwụgwọ antiretroviral dị elu, nke belatara ọnụ ọgụgụ ndị ọrịa nke ukwuu, na 2002 na 2006, Novartis kagburu ikike ahịa nke ọgwụ Fomivirsen na Europe na United States n'otu n'otu, ma kwụsịtụrụ ngwaahịa ahụ n'ahịa.

Mipomersen sodium (aha ahia Kynamro) bụ ọgwụ ASO nke ụlọ ọrụ French Genzyme mepụtara.Na Jenụwarị 2013, FDA kwadoro ya maka ọgwụgwọ hypercholesterolemia familial homozygous.Mipomersen na-egbochi nkwupụta nke ApoB-100 protein (apolipoprotein) site na ijikọ na ApoB-100mRNA, si otú ahụ na-ebelata cholesterol dị ala nke mmadụ, lipoprotein dị ala na ihe ndị ọzọ na-egosi, ma n'ihi mmetụta ndị dị ka imeju imeju, December 13, 2012, a na-ere akwụkwọ ikike maka otu ụbọchị ahụ.

Na Septemba 2016, FDA kwadoro Eteplirsen (aha ahia Exon 51) nke Sarepta mepụtara maka ọgwụgwọ Duchenne muscular dystrophy (DMD).Ndị ọrịa DMD enweghị ike ịkọwapụta protein anti-atrophic na-arụ ọrụ n'ihi mmụgharị na mkpụrụ ndụ DMD n'ime ahụ.Eteplirsen kpọmkwem jikọtara exon 51 nke tupu ozi RNA (Pre-mRNA) nke protein, wepụ exon 51, na-weghachi ụfọdụ downstream genes The nkịtị okwu nke, transcription na nsụgharị iji nweta akụkụ nke dystrophin, iji nweta ọgwụgwọ mmetụta.

Nusinersen bụ ọgwụ ASO nke Spinraza mepụtara maka ọgwụgwọ nke atrophy muscular spinal ma kwadoro ya na FDA na December 23, 2016. Na 2018, Inotesen mepụtara site na Tegsedi maka ọgwụgwọ nke transthyretin amyloidosis nke ndị okenye na FDA kwadoro.Na 2019, Golodirsen, nke Sarepta mepụtara maka ọgwụgwọ nke muscular dystrophy nke Duchenne, bụ FDA kwadoro.O nwere otu usoro ihe eji eme ihe dị ka Eteplirsen, ebe ọrụ ya na-aghọ exon 53. N'otu afọ ahụ, Volanesorsen, nke Ionisand Akcea jikọtara maka ọgwụgwọ hyperchylomicronemia ezinụlọ, kwadoro site na European Medicines Agency (EMA).Volanesorsen na-achịkwa metabolism triglyceride site na igbochi mmepụta nke apolipoprotein C-Ⅲ, mana ọ nwekwara mmetụta dị n'ibelata ọkwa platelet.

Defibrotide bụ ngwakọta oligonucleotide nwere njirimara plasmin nke Jazz mepụtara.Ọ nwere 90% DNA otu eriri DNA yana 10% DNA nwere eriri abụọ.EMA kwadoro ya na 2013 ma emesịa kwadoro ya site na FDA maka ọgwụgwọ nke nnukwu akwara imeju.Ọrịa na-adịghị mma.Defibrotide nwere ike ịbawanye ọrụ nke plasmin, mụbaa plasminogen activator, kwalite nhazi nke thrombomodulin, ma belata okwu nke von Willebrand factor na plasminogen activator inhibitors iji nweta mmetụta ọgwụgwọ.

siRNA     

siRNA bụ obere iberibe RNA nwere ogologo ogologo na usoro emepụtara site na igbubi RNA ebumnuche.Ndị siRNA ndị a nwere ike bute mmebi nke mRNA ebumnuche ma nweta mmetụta nkwụsị nke mkpụrụ ndụ ihe nketa.E jiri ya tụnyere obere ọgwụ molekul kemịkalụ, mkpụrụ ndụ ihe na-eme ka ọ kwụsịlata nke ọgwụ siRNA nwere nkọwapụta na arụmọrụ dị elu.

N'August 11, 2018, FDA kwadoro patisiran ọgwụ siRNA mbụ (aha ahia Onpattro) wee malite ọrụ ya.Nke a bụ otu n'ime isi ihe dị mkpa na akụkọ mmepe nke teknụzụ nnyonye anya RNA.Alnylam na Genzyme, onye enyemaka Sanofi mebere Patisiran.Ọ bụ ọgwụ siRNA maka ọgwụgwọ nke amyloidosis mediated thyroxine.N'afọ 2019, FDA kwadoro givosiran (aha ahia Givlaari) dị ka ọgwụ siRNA nke abụọ maka ọgwụgwọ nnukwu ọrịa imeju na ndị okenye.N'afọ 2020, Alnylam mepụtara ọgwụ izizi ụdị I maka ọgwụgwọ ụmụaka na ndị okenye.Lumasiran nwere nnukwu oxaluria bụ FDA kwadoro.Na Disemba 2020, EMA kwadoro Inclisiran, nke Novartis na Alnylam jikọrọ aka maka ọgwụgwọ hypercholesterolemia okenye ma ọ bụ dyslipidemia agwakọta.

Aptamer

Nucleic acid aptamers bụ oligonucleotides nke nwere ike jikọta na ụdị ihe dị iche iche ezubere iche dị ka obere ụmụ irighiri mmiri, DNA, RNA, polypeptides ma ọ bụ protein nwere njikọ dị elu na nkọwapụta.E jiri ya tụnyere ọgwụ nje, nucleic acid aptamers nwere njirimara nke njikọ dị mfe, ọnụ ala dị ala na ọtụtụ ebumnuche dị iche iche, ma nwee ikike dị ukwuu maka ngwa ọgwụ na nchọpụta ọrịa, ọgwụgwọ na mgbochi.

Pegaptanib bụ ọgwụ mbụ nucleic acid aptamer nke Valeant mepụtara maka ọgwụgwọ nke afọ mmiri metụtara macular degeneration na FDA kwadoro ya na 2004. E mesịa, EMA na PMDA kwadoro ya na January 2006 na July 2008 wee gaa n'ahịa.Pegaptanib na-egbochi angiogenesis site na nchikota nke oghere oghere na ihe uto endothelial vaskụla iji nweta mmetụta ọgwụgwọ.Kemgbe ahụ, ọ zutere asọmpi sitere na ọgwụ ndị yiri ya bụ Lucentis, òkè ahịa ya agbadala nke ukwuu.

Ọgwụ Nucleic acid abụrụla ebe na-ekpo ọkụ na ọgwụ ụlọ ọgwụ na ahịa ọgwụ ọhụrụ n'ihi mmetụta ọgwụgwọ ha dị ịrịba ama na okirikiri mmepe dị mkpụmkpụ.Dị ka ọgwụ na-apụta, ọ na-eche ihe ịma aka ihu mgbe ọ na-eche ohere ihu.N'ihi njirimara exogenous ya, nkọwapụta, nkwụsi ike na nnyefe dị irè nke acid nucleic aghọwo ihe bụ isi maka ikpebi ma oligonucleotides nwere ike ịghọ ọgwụ nucleic acid dị irè nke ukwuu.Mmetụta ndị a na-atụghị anya ya na-abụkarị isi ihe ọgwụ nucleic acid na-enweghị ike ileghara ya anya.Otú ọ dị, ọgwụ nucleic acid nwere ike imetụta nkwupụta nke mkpụrụ ndụ ihe nketa na-akpata ọrịa sitere na mgbọrọgwụ, ma nwee ike nweta usoro nhazi usoro na ọkwa otu-isi, nke nwere njirimara nke "ịgwọ ihe kpatara ya na ịgwọ ihe mgbaàmà".N'ihi mgbanwe nke ọrịa na-arịwanye elu, ọ bụ naanị ọgwụgwọ mkpụrụ ndụ ihe nketa nwere ike nweta nsonaazụ na-adịgide adịgide.Site na mmụba na-aga n'ihu, izu oke na ọganihu nke teknụzụ ndị metụtara ya, ọgwụ nucleic acid nke antisense nucleic acids, siRNA, na nucleic acid aptamers nọchitere anya ga-ewelite ọhụhụ ọhụrụ na ọgwụgwọ ọrịa na ụlọ ọrụ ọgwụ.

Rmmetụta:

[1] Liu Shaojin, Feng Xuejiao, Wang Junshu, Xiao Zhengqiang, Cheng Pingsheng.Nyocha ahịa nke ọgwụ nucleic acid na obodo m na ihe mgbochi[J].Akwụkwọ akụkọ Chinese nke Biological Engineering, 2021, 41 (07): 99-109.

[2] Chen Wenfei, Wu Fuhua, Zhang Zhirong, Sun Xun.Ọganihu nyocha na nkà mmụta ọgwụ nke ọgwụ nucleic acid a na-ere ahịa[J].Akwụkwọ akụkọ Chinese nke ọgwụ, 2020, 51 (12): 1487-1496.

[3] Wang Jun, Wang Lan, Lu Jiazhen, Huang Zhen.Nyocha nke nrụpụta ọrụ na ọganihu nyocha nke ọgwụ nucleic acid a na-ere ahịa[J].Akwụkwọ akụkọ Chinese nke ọgwụ ọhụrụ, 2019, 28 (18): 2217-2224.

Banyere onye edemede: Sha Luo, onye nyocha ọgwụ na ndị ọrụ mmepe nke China, na-arụ ọrụ ugbu a maka nnukwu ụlọ ọrụ nyocha ọgwụ na mmepe ụlọ, na-agba mbọ na nyocha na mmepe nke ọgwụ ndị China ọhụrụ.

Ngwaahịa ndị emetụtara:

Ngwa Cell Direct RT-qPCR