Me ka hoʻomohala mau ʻana o ka ʻenehana biology molecular, ua loaʻa ka pilina ma waena o nā hoʻololi gene a me nā hemahema a me nā maʻi i ka ʻike hohonu.Ua ʻike nui ʻia nā ʻakika nucleic ma muli o ko lākou hiki ke hoʻohana i ka maʻi a me ka mālama ʻana i nā maʻi.ʻO nā lāʻau lapaʻau nucleic acid e pili ana i ka DNA synthesized artificially a i ʻole nā ​​ʻāpana RNA me nā hana lapaʻau maʻi.Hiki i ia mau lāʻau lapaʻau ke hana pololei i nā genes i hoʻokumu ʻia i ka maʻi a i ʻole nā ​​mRNA i hoʻokumu ʻia i ka maʻi, a pāʻani i ka hana i ka mālama ʻana i nā maʻi ma ka pae gene.Ke hoʻohālikelike ʻia me nā lāʻau lapaʻau liʻiliʻi liʻiliʻi a me nā lāʻau antibody, hiki i nā lāʻau nucleic acid ke hoʻoponopono i ka hōʻike ʻana o nā genes kumu maʻi mai ke aʻa, a loaʻa nā ʻano o ka "mālama ʻana i nā hōʻailona a hoʻōla i ke kumu kumu".Loaʻa i nā lāʻau lapaʻau nucleic acid nā pōmaikaʻi e like me ka hana kiʻekiʻe, haʻahaʻa haʻahaʻa, a me ka kikoʻī kiʻekiʻe.Mai ka hoʻomaka ʻana o ka lāʻau nucleic acid fomivirsen sodium i ka makahiki 1998, ua ʻae ʻia ka nui o nā lāʻau nucleic acid no ka mālama ʻana.

ʻO nā lāʻau lapaʻau nucleic acid i kēia manawa ma ka mākeke honua ka nui o ka antisense nucleic acid (ASO), RNA interfering liʻiliʻi (siRNA), a me nā aptamers nucleic acid.Ma waho aʻe o nā aptamers nucleic acid (ʻoi aku paha ma mua o 30 nucleotides), ʻo nā lāʻau lapaʻau nucleic acid ka mea maʻamau o nā oligonucleotides i haku ʻia me 12 a 30 mau nucleotides, ʻike ʻia hoʻi nā lāʻau oligonucleotide.Eia kekahi, ua hōʻike pū nā miRNA, ribozymes a me deoxyribozymes i ka waiwai hoʻomohala nui i ka mālama ʻana i nā maʻi like ʻole.Ua lilo nā lāʻau lapaʻau nucleic i hoʻokahi o nā kahua hoʻohiki i ka noiʻi a me ka hoʻomohala ʻana o ka biomedicine i kēia lā.

Nā laʻana o nā lāʻau lapaʻau nucleic acid i ʻāpono ʻia

Antisense nucleic acid

ʻO ka ʻenehana Antisense kahi ʻenehana hoʻomohala lāʻau hou e pili ana i ke kumu o Watson-Crick base complementation, me ka hoʻohana ʻana i nā ʻāpana DNA a i ʻole nā ​​ʻāpana RNA i hoʻohui ʻia a i ʻole synthesized e ke kino e hoʻoponopono pono i ka hōʻike ʻana o nā genes.Loaʻa i ka antisense nucleic acid kahi kaʻina kumu i hoʻohui ʻia i ka RNA i manaʻo ʻia a hiki ke hoʻopaʻa pono iā ia.ʻO nā ʻakika nucleic antisense maʻamau ka DNA antisense, antisense RNA a me ribozymes.Ma waena o lākou, ma muli o nā hiʻohiʻona o ke kūpaʻa kiʻekiʻe a me ke kumukūʻai haʻahaʻa o ka DNA antisense, aia ka antisense DNA i kahi kūlana koʻikoʻi i ka noiʻi a me ka noi ʻana o nā lāʻau antisense nucleic acid.

Hoʻokumu ʻia ka sodium Fomivirsen (inoa kālepa Vitravene) e Ionis Novartis.I ʻAukake 1998, ua ʻae ka FDA no ka mālama ʻana i ka cytomegalovirus retinitis i nā maʻi immunocompromised (ʻoi aku ka nui o nā maʻi AIDS), e lilo ana i lāʻau nucleic acid mua e kūʻai ʻia.Hoʻopaʻa ʻo Fomivirsen i ka hōʻike protein hapa o CMV ma o ka hoʻopaʻa ʻana i ka mRNA kikoʻī (IE2), a laila e hoʻoponopono i ka hōʻike ʻana o nā genes viral e hoʻokō i nā hopena therapeutic.Eia naʻe, ma muli o ka puka ʻana o ka antiretroviral therapy kiʻekiʻe, i hoʻemi nui i ka helu o nā maʻi, ma 2002 a me 2006, ua kāpae ʻo Novartis i ka ʻae ʻana o ka mākeke o Fomivirsen lāʻau ma ʻEulopa a me ʻAmelika Hui Pū ʻIa, a ua hoʻokuʻu ʻia ka huahana mai ka mākeke.

ʻO ka sodium Mipomersen (inoa kālepa ʻo Kynamro) kahi lāʻau ASO i hoʻomohala ʻia e ka hui Farani Genzyme.I Ianuali 2013, ua ʻae ka FDA no ka mālama ʻana i ka hypercholesterolemia ʻohana homozygous.Hoʻopaʻa ʻo Mipomersen i ka hōʻike ʻana o ka protein ApoB-100 (apolipoprotein) ma o ka hoʻopaʻa ʻana iā ApoB-100mRNA, a laila e hōʻemi nui ana i ke kanaka lipoprotein cholesterol haʻahaʻa haʻahaʻa, lipoprotein haʻahaʻa haʻahaʻa a me nā mea hōʻailona ʻē aʻe, akā ma muli o nā hopena ʻaoʻao e like me ka ʻawaʻawa o ke akepaʻa, December 13, 2012 No ke kūʻai aku ʻana i ka lāʻau lapaʻau.

I Kepakemapa 2016, Eteplirsen (inoa kālepa Exon 51) i hoʻomohala ʻia e Sarepta no ka mālama ʻana i ka Duchenne muscular dystrophy (DMD) i ʻae ʻia e ka FDA.ʻAʻole hiki i nā poʻe maʻi DMD ke hōʻike maʻamau i ka protein anti-atrophic hana ma muli o ka hoʻololi ʻana i ka gene DMD i ke kino.Hoʻopili pono ʻo Eteplirsen i ka exon 51 o ka RNA mua (Pre-mRNA) o ka protein, wehe i ka exon 51, a hoʻihoʻi i kekahi mau genes downstream ʻO ka ʻōlelo maʻamau o, transcription a me ka unuhi ʻana e loaʻa kahi hapa o ka dystrophin, i mea e hoʻokō ai i ka hopena therapeutic.

ʻO Nusinersen kahi lāʻau ASO i hoʻomohala ʻia e Spinraza no ka mālama ʻana i ka spinal muscular atrophy a ua ʻae ʻia e ka FDA ma Dekemaba 23, 2016. Ma 2018, ʻo Inotesen i hoʻomohala ʻia e Tegsedi no ka mālama ʻana i ka amyloidosis transthyretin hereditary makua i ʻae ʻia e ka FDA.I ka makahiki 2019, ua ʻae ʻia ʻo Golodirsen, i hoʻomohala ʻia e Sarepta no ka mālama ʻana o Duchenne muscular dystrophy, e ka FDA.Loaʻa iā ia ka hana like me Eteplirsen, a lilo kona kahua o ka hana i exon 53. I ka makahiki hoʻokahi, Volanesorsen, hui pū ʻia e Ionisand Akcea no ka mālama ʻana i ka hyperchylomicronemia ʻohana, ua ʻae ʻia e ka European Medicines Agency (EMA).Hoʻoponopono ʻo Volanesorsen i ka metabolism triglyceride ma ke kāohi ʻana i ka hana ʻana o ka apolipoprotein C-Ⅲ, akā loaʻa pū kekahi i ka hopena o ka hoʻohaʻahaʻa ʻana i nā pae platelet.

ʻO Defibrotide kahi hui oligonucleotide me nā waiwai plasmin i hoʻomohala ʻia e Jazz.Loaʻa iā ia he 90% DNA stranded single-stranded a me 10% DNA double-stranded.Ua ʻae ʻia e ka EMA i ka makahiki 2013 a ua ʻae ʻia e ka FDA no ka mālama ʻana i nā veins hepatic koʻikoʻi.ʻO ka maʻi occlusive.Hiki i ka Defibrotide ke hoʻonui i ka hana o ka plasmin, hoʻonui i ka plasminogen activator, hoʻoikaika i ka hoʻoponopono ʻana o ka thrombomodulin, a hoʻemi i ka hōʻike ʻana o von Willebrand factor a me plasminogen activator inhibitors e hoʻokō i nā hopena therapeutic.

siRNA     

ʻO siRNA kahi ʻāpana liʻiliʻi o RNA me kahi lōʻihi kikoʻī a me ke kaʻina i hana ʻia e ka ʻoki ʻana i ka RNA i manaʻo ʻia.Hiki i kēia mau siRNA ke hoʻoulu i ka hoʻohaʻahaʻa ʻana o ka mRNA target a loaʻa i nā hopena silencing gene.Hoʻohālikelike ʻia me nā lāʻau mole liʻiliʻi liʻiliʻi, ʻo ka hopena silencing gene o nā lāʻau siRNA he kikoʻī kiʻekiʻe a me ka pono.

Ma ʻAukake 11, 2018, ua ʻae ʻia ka lāʻau lapaʻau siRNA patisiran (inoa kālepa Onpattro) e ka FDA a hoʻokuʻu ʻia.ʻO kēia kekahi o nā mea nui i ka mōʻaukala hoʻomohala o ka ʻenehana interference RNA.Ua hoʻomohala ʻia ʻo Patisiran e Alnylam a me Genzyme, kahi hui o Sanofi.He lāʻau lapaʻau siRNA no ka mālama ʻana i ka amyloidosis hoʻoilina thyroxine-mediated.I ka makahiki 2019, ua ʻae ʻia ʻo Givosiran (inoa kālepa ʻo Givlaari) e ka FDA ma ke ʻano he lua siRNA lāʻau no ka mālama ʻana i ka porphyria hepatic acute i nā pākeke.I ka makahiki 2020, ua hoʻomohala ʻo Alnylam i kahi lāʻau lapaʻau ʻano mua no ka mālama ʻana i nā keiki a me nā pākeke.Ua ʻae ʻia ʻo Lumasiran me ka oxaluria kiʻekiʻe e ka FDA.I Kekemapa 2020, Inclisiran, i hoʻomohala ʻia e Novartis a me Alnylam no ka mālama ʻana i ka hypercholesterolemia makua a i ʻole dyslipidemia hui ʻia, ua ʻae ʻia e ka EMA.

Aptamer

ʻO nā aptamers nucleic acid he oligonucleotides e hiki ke hoʻopaʻa i nā ʻano molekole i hoʻopaʻa ʻia e like me nā molekele liʻiliʻi liʻiliʻi, DNA, RNA, polypeptides a i ʻole nā ​​​​protein me ka pilina kiʻekiʻe a me ka kikoʻī.Ke hoʻohālikelike ʻia me nā antibodies, loaʻa nā aptamers nucleic acid i nā hiʻohiʻona o ka synthesis maʻalahi, ke kumukūʻai haʻahaʻa a me ka laulā ākea o nā pahuhopu, a loaʻa i kahi ākea ākea no ka noi lāʻau i ka maʻi maʻi, mālama a me ka pale ʻana.

ʻO Pegaptanib ka lāʻau nucleic acid aptamer mua i hoʻomohala ʻia e Valeant no ka mālama ʻana i ka degeneration macular e pili ana i ka makahiki a ua ʻae ʻia e ka FDA ma 2004. Ma hope mai, ua ʻae ʻia e EMA a me PMDA i Ianuali 2006 a me Iulai 2008 a hele ma ka mākeke.Kāohi ʻo Pegaptanib i ka angiogenesis ma o ka hui pū ʻana o ka hoʻolālā spatial a me ka mea ulu endothelial vascular e hoʻokō i nā hopena therapeutic.Mai ia manawa, ua hālāwai ʻo ia i ka hoʻokūkū mai nā lāʻau like ʻo Lucentis, a ua hāʻule nui kāna māhele mākeke.

Ua lilo nā lāʻau lapaʻau nucleic i wahi wela i ka lāʻau lapaʻau lapaʻau a me ka mākeke lāʻau hou ma muli o kā lākou hopena curative kupaianaha a me ka pōkole hoʻomohala pōkole.Ma ke ʻano he lāʻau lapaʻau e kū mai ana, ke kū nei i nā pilikia i ka wā e kū ana i nā manawa kūpono.Ma muli o kāna mau hiʻohiʻona exogenous, ʻo ke kikoʻī, ka paʻa a me ka hāʻawi maikaʻi ʻana o nā waikawa nucleic i lilo i kumu nui no ka hoʻoholo ʻana inā hiki i ka oligonucleotides ke lilo i mau lāʻau nucleic acid maikaʻi loa.ʻO nā hopena paʻa ʻole he wahi koʻikoʻi o nā lāʻau lapaʻau nucleic acid ʻaʻole hiki ke mālama ʻia.Eia nō naʻe, hiki i nā lāʻau nucleic acid ke hoʻopili i ka hōʻike ʻana i nā genes kumu mai ke kumu, a hiki ke hoʻokō i ka kikoʻī kikoʻī ma ka pae hoʻokahi, nona nā hiʻohiʻona o "ka mālama ʻana i ke kumu kumu a mālama i nā hōʻailona".I ka nānā ʻana i ka ʻokoʻa o nā maʻi hou aʻe, hiki i ka mālama genetic wale nō ke loaʻa nā hopena mau loa.Me ka hoʻomau mau ʻana, ka maikaʻi a me ka holomua o nā ʻenehana pili, nā lāʻau nucleic acid i hōʻike ʻia e nā antisense nucleic acids, siRNA, a me nā nucleic acid aptamers e hoʻomaka i kahi nalu hou i ka mālama ʻana i nā maʻi a me ka ʻoihana lāʻau.

References:

[1] Liu Shaojin, Feng Xuejiao, Wang Junshu, Xiao Zhengqiang, Cheng Pingsheng.Ka nānā ʻana o ka mākeke o nā lāʻau nucleic acid ma koʻu ʻāina a me nā mea kūʻē [J].Ka Nupepa Kina o Biological Engineering, 2021, 41(07): 99-109.

[2] Chen Wenfei, Wu Fuhua, Zhang Zhirong, Sun Xun.Ka holomua o ka noiʻi ʻana i ka lāʻau lapaʻau o nā lāʻau ʻakika nucleic i kūʻai ʻia [J].Puke Lapaʻau Pākē, 2020, 51(12): 1487-1496.

[3] Wang Jun, Wang Lan, Lu Jiazhen, Huang Zhen.Ka nānā 'ana i ka maika'i a me ka holomua noi'i o nā lā'au 'akika nucleic market i kū'ai 'ia [J].Ka Nupepa Haina o na Laau Laau Hou, 2019, 28(18): 2217-2224.

No ka mea kākau: ʻO Sha Luo, he limahana noiʻi a me ka hoʻomohala ʻana i ka lāʻau lapaʻau Kina, ke hana nei i kēia manawa no kahi hui noiʻi nui a me ka hoʻomohala ʻana i ka lāʻau lapaʻau, a ua kūpaʻa ʻo ia i ka noiʻi a me ka hoʻomohala ʻana i nā lāʻau lapaʻau Kina hou.

Nā huahana pili:

Kelepona pololei RT-qPCR kime