{"id":11467,"date":"2024-07-09T10:53:56","date_gmt":"2024-07-09T03:23:56","guid":{"rendered":"https:\/\/abtvn.com\/?p=11467"},"modified":"2025-08-06T12:25:55","modified_gmt":"2025-08-06T04:55:55","slug":"oligonucleotide-tri-lieu-ung-dung-nhu-the-nao","status":"publish","type":"post","link":"https:\/\/abtvn.com\/en\/oligonucleotide-tri-lieu-ung-dung-nhu-the-nao\/","title":{"rendered":"Oligonucleotide \u1ee9ng d\u1ee5ng trong tr\u1ecb li\u1ec7u nh\u01b0 th\u1ebf n\u00e0o?<\/strong>"},"content":{"rendered":"

Oligonucleotide tr\u1ecb li\u1ec7u <\/strong>\u0111ang \u0111\u01b0\u1ee3c quan t\u00e2m v\u1edbi nhi\u1ec1u ti\u1ec1m n\u0103ng cung c\u1ea5p c\u00e1c ph\u01b0\u01a1ng ph\u00e1p \u0111i\u1ec1u tr\u1ecb cho c\u00e1c b\u1ec7nh di truy\u1ec1n v\u00e0\/ho\u1eb7c c\u00e1c b\u1ec7nh hi\u1ebfm g\u1eb7p. Nh\u1eefng tr\u00ecnh t\u1ef1 oligonucleotide DNA ho\u1eb7c RNA<\/a><\/strong> n\u00e0y \u0111\u00e3 c\u00e1ch m\u1ea1ng h\u00f3a l\u0129nh v\u1ef1c y h\u1ecdc hi\u1ec7n \u0111\u1ea1i. B\u00e0i vi\u1ebft n\u00e0y s\u1ebd cung c\u1ea5p nh\u1eefng th\u00f4ng tin xoay quanh oligonucleotide tr\u1ecb li\u1ec7u, c\u00e1ch ch\u00fang ho\u1ea1t \u0111\u1ed9ng v\u00e0 c\u00e1c \u1ee9ng d\u1ee5ng ti\u1ec1m n\u0103ng c\u1ee7a ch\u00fang, \u0111\u1eb7c bi\u1ec7t t\u1eadp trung v\u00e0o s\u1ef1 \u0111\u00f3ng g\u00f3p c\u1ee7a oligonucleotide trong vi\u1ec7c ph\u00e1t tri\u1ec3n c\u00e1c li\u1ec7u ph\u00e1p \u0111i\u1ec1u tr\u1ecb v\u00e0 ch\u1ea9n \u0111o\u00e1n.<\/p>\n\n\n\n

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Oligonucleotide tr\u1ecb li\u1ec7u l\u00e0 g\u00ec?<\/strong><\/h2>\n\n\n\n

C\u00e1c oligonucleotide tr\u1ecb li\u1ec7u l\u00e0 c\u00e1c ph\u00e2n t\u1eed DNA ho\u1eb7c RNA \u0111\u01b0\u1ee3c thi\u1ebft k\u1ebf \u0111\u1eb7c bi\u1ec7t \u0111\u1ec3 t\u01b0\u01a1ng t\u00e1c v\u1edbi v\u1eadt li\u1ec7u di truy\u1ec1n c\u1ee7a t\u1ebf b\u00e0o nh\u1eb1m t\u1ea1o ra t\u00e1c d\u1ee5ng ch\u1eefa b\u1ec7nh trong c\u01a1 th\u1ec3. Kh\u00f4ng gi\u1ed1ng nh\u01b0 c\u00e1c lo\u1ea1i thu\u1ed1c th\u00f4ng th\u01b0\u1eddng nh\u1eafm v\u00e0o protein ho\u1eb7c enzyme, c\u00e1c oligonucleotide tr\u1ecb li\u1ec7u ho\u1ea1t \u0111\u1ed9ng \u1edf c\u1ea5p \u0111\u1ed9 di truy\u1ec1n, \u0111i\u1ec1u ch\u1ec9nh bi\u1ec3u hi\u1ec7n c\u1ee7a c\u00e1c gen c\u1ee5 th\u1ec3. C\u00e1c oligonucleotide n\u00e0y c\u00f3 th\u1ec3 c\u00f3 nhi\u1ec1u d\u1ea1ng kh\u00e1c nhau, ch\u1eb3ng h\u1ea1n nh\u01b0 Antisense oligonucleotide (ASO), RNA can thi\u1ec7p nh\u1ecf (siRNA)<\/strong> or microRNA (miRNA)<\/strong>. Nh\u1eefng ph\u00e2n t\u1eed oligonucleotide n\u00e0y \u0111\u00e3 tr\u1edf th\u00e0nh v\u0169 kh\u00ed m\u1ea1nh m\u1ebd ch\u1ed1ng l\u1ea1i c\u00e1c b\u1ec7nh di truy\u1ec1n v\u00e0 c\u00e1c b\u1ec7nh r\u1ed1i lo\u1ea1n hi\u1ebfm g\u1eb7p kh\u00e1c.<\/p>\n\n\n\n

\"H\u00ecnh
Figure 1.<\/strong> C\u00e1c d\u1ea1ng oligonucleotide trong tr\u1ecb li\u1ec7u<\/em><\/figcaption><\/figure>\n\n\n\n
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2. Oligonucleotide tr\u1ecb li\u1ec7u ho\u1ea1t \u0111\u1ed9ng nh\u01b0 th\u1ebf n\u00e0o?<\/strong><\/h2>\n\n\n\n

Ch\u00eca kh\u00f3a \u0111\u1ec3 hi\u1ec3u c\u00e1ch th\u1ee9c ho\u1ea1t \u0111\u1ed9ng c\u1ee7a oligonucleotide tr\u1ecb li\u1ec7u n\u1eb1m \u1edf kh\u1ea3 n\u0103ng can thi\u1ec7p v\u00e0o s\u1ef1 bi\u1ec3u hi\u1ec7n c\u1ee7a c\u00e1c gen c\u1ee5 th\u1ec3. C\u00e1c b\u1ec7nh di truy\u1ec1n th\u01b0\u1eddng l\u00e0 k\u1ebft qu\u1ea3 c\u1ee7a vi\u1ec7c s\u1ea3n xu\u1ea5t protein b\u1ea5t th\u01b0\u1eddng do tr\u00ecnh t\u1ef1 gen b\u1ecb l\u1ed7i. C\u00e1c oligonucleotide tr\u1ecb li\u1ec7u \u0111\u01b0\u1ee3c thi\u1ebft k\u1ebf \u0111\u1ec3 \u0111i\u1ec1u ch\u1ec9nh ho\u1eb7c thay \u0111\u1ed5i qu\u00e1 tr\u00ecnh s\u1ea3n xu\u1ea5t c\u00e1c protein b\u1ea5t th\u01b0\u1eddng n\u00e0y. C\u00e1c ph\u01b0\u01a1ng ph\u00e1p \u0111i\u1ec1u tr\u1ecb ch\u00ednh d\u1ef1a tr\u00ean oligonucleotide bao g\u1ed3m:<\/p>\n\n\n\n

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2.1. Antisense Oligonucleotide (ASO)<\/strong><\/h3>\n\n\n\n

Antisense Oligonucleotide<\/strong> hay ASO l\u00e0 nh\u1eefng ph\u00e2n t\u1eed oligonucleotide ng\u1eafn, m\u1ea1ch \u0111\u01a1n c\u00f3 chi\u1ec1u d\u00e0i t\u1eeb 15 \u2013 22 nucleotide, \u0111\u01b0\u1ee3c thi\u1ebft k\u1ebf \u0111\u1ec3 li\u00ean k\u1ebft v\u1edbi c\u00e1c tr\u00ecnh t\u1ef1 RNA m\u1ee5c ti\u00eau m\u00e3 h\u00f3a protein c\u0169ng nh\u01b0 c\u00e1c RNA kh\u00f4ng m\u00e3 h\u00f3a. \u00a0D\u1ef1a tr\u00ean c\u01a1 ch\u1ebf ho\u1ea1t \u0111\u1ed9ng c\u1ee7a ASO v\u1edbi tr\u00ecnh t\u1ef1 RNA m\u1ee5c ti\u00eau, ASO c\u00f3 th\u1ec3 \u0111\u01b0\u1ee3c chia th\u00e0nh c\u00e1c lo\u1ea1i bao g\u1ed3m: ASO ph\u00e2n h\u1ee7y RNA (RNA degradation) v\u00e0 ASO c\u1ea3n tr\u1edf.<\/p>\n\n\n\n

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(A) ASO ph\u00e2n h\u1ee7y RNA qua trung gian enzyme RNase H: <\/strong>c\u00e1c enzyme RNase H n\u00e0y c\u00f3 ch\u1ee9c n\u0103ng x\u00fac t\u00e1c qu\u00e1 tr\u00ecnh ph\u00e2n h\u1ee7y RNA \u1edf c\u00e1c tr\u00ecnh t\u1ef1 m\u1ea1ch \u0111\u00f4i lai gi\u1eefa DNA v\u00e0 RNA. H\u1ea7u h\u1ebft c\u00e1c thu\u1ed1c antisense \u0111\u1ec1u ho\u1ea1t \u0111\u1ed9ng th\u00f4ng qua c\u01a1 ch\u1ebf ph\u1ee5 thu\u1ed9c RNase H. C\u00e1c ASO ph\u1ee5 thu\u1ed9c v\u00e0o RNase H th\u00f4ng th\u01b0\u1eddng \u0111\u01b0\u1ee3c thi\u1ebft k\u1ebf \u0111\u1ec3 li\u00ean k\u1ebft v\u1edbi tr\u00ecnh t\u1ef1 RNA m\u1ee5c ti\u00eau \u0111\u1ec3 t\u1ea1o th\u00e0nh tr\u00ecnh t\u1ef1 m\u1ea1ch \u0111\u00f4i lai gi\u1eefa ASO-RNA t\u1eeb \u0111\u00f3 enzyme RNase H s\u1ebd ph\u00e2n h\u1ee7y v\u00e0 l\u00e0m suy gi\u1ea3m RNA m\u1ee5c ti\u00eau \u0111\u01b0\u1ee3c ASO li\u00ean k\u1ebft. \u00a0K\u1ebft qu\u1ea3 ph\u00e2n c\u1eaft, suy gi\u1ea3m c\u1ee7a RNA m\u1ee5c ti\u00eau c\u00f3 th\u1ec3 \u0111\u01b0\u1ee3c ki\u1ec3m tra b\u1eb1ng k\u1ef9 thu\u1eadt RT-qPCR ho\u1eb7c RNA-seq. H\u1ea7u h\u1ebft c\u00e1c lo\u1ea1i thu\u1ed1c antisense \u0111\u00e3 \u0111\u01b0\u1ee3c FDA ch\u1ea5p thu\u1eadn \u0111\u1ec1u th\u00f4ng qua c\u01a1 ch\u1ebf n\u00e0y. M\u1ed9t s\u1ed1 ASO li\u00ean quan \u0111\u1ebfn c\u01a1 ch\u1ebf n\u00e0y \u0111\u00e3 \u0111\u01b0\u1ee3c FDA ph\u00ea duy\u1ec7t bao g\u1ed3m: Fomivirsen, Mipomersen, Inotersen, Vutrisiran, Volanesorsen, Tofersen.<\/p>\n\n\n\n

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(B) ASO c\u1ea3n tr\u1edf kh\u00f4ng gian (Steric-hindrance):<\/strong> Ngo\u00e0i c\u01a1 ch\u1ebf ph\u00e2n c\u1eaft, suy gi\u1ea3m RNA th\u00f4ng qua enzyme RNase H, c\u00e1c ASO n\u00e0y c\u0169ng c\u00f3 th\u1ec3 li\u00ean k\u1ebft v\u1edbi RNA m\u1ee5c ti\u00eau t\u1eeb \u0111\u00f3 ng\u0103n ch\u1eb7n c\u1ea3n tr\u1edf s\u1ef1 t\u01b0\u01a1ng t\u00e1c gi\u1eefa RNA m\u1ee5c ti\u00eau v\u1edbi c\u00e1c ph\u00e2n t\u1eed kh\u00e1c trong t\u1ebf b\u00e0o. C\u00e1c ASO ch\u1eb7n kh\u00f4ng gian nh\u1eafm m\u1ee5c ti\u00eau v\u00e0o c\u00e1c ph\u1ea7n t\u1eed c\u1ee7a RNA nh\u01b0 v\u00f9ng 5\u02b9-UTR c\u1ee7a mRNA c\u00f3 th\u1ec3 \u0111\u01b0\u1ee3c li\u00ean k\u1ebft \u0111\u1ec3 \u0111i\u1ec1u ch\u1ec9nh t\u0103ng ho\u1eb7c gi\u1ea3m d\u1ecbch m\u00e3 protein. V\u00ed d\u1ee5, c\u00e1c ASO tr\u00f9ng l\u1eb7p (overlap) ho\u1eb7c g\u1ea7n v\u1edbi codon kh\u1edfi \u0111\u1ea7u c\u1ee7a mRNA c\u00f3 th\u1ec3 ng\u0103n ch\u1eb7n s\u1ef1 li\u00ean k\u1ebft ho\u1eb7c l\u1eafp r\u00e1p c\u1ee7a ribosome tr\u00ean mRNA t\u1eeb \u0111\u00f3 l\u00e0m gi\u1ea3m qu\u00e1 tr\u00ecnh d\u1ecbch m\u00e3. Ngo\u00e0i ra, c\u00e1c ASO nh\u1eafm m\u1ee5c ti\u00eau v\u00e0o c\u00e1c ph\u1ea7n t\u1eed kh\u00e1c, nh\u01b0 khung \u0111\u1ecdc m\u1edf ng\u01b0\u1ee3c d\u00f2ng (upstream open reading frame – uORF) ho\u1eb7c c\u1ea5u tr\u00fac k\u1eb9p t\u00f3c trong 5\u02b9-UTR, c\u00f3 th\u1ec3 n\u00e2ng cao kh\u1ea3 n\u0103ng d\u1ecbch m\u00e3 c\u1ee7a gene. M\u1ed9t s\u1ed1 ASO li\u00ean quan \u0111\u1ebfn c\u01a1 ch\u1ebf c\u1ea3n tr\u1edf kh\u00f4ng gian \u0111\u00e3 \u0111\u01b0\u1ee3c FDA ph\u00ea duy\u1ec7t c\u00f3 th\u1ec3 k\u1ec3 \u0111\u1ebfn l\u00e0: Eteplirsen, Nusinersen, Golodirsen, Viltolanersen, Casimersen.<\/p>\n\n\n\n

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\"H\u00ecnh
Figure 2. <\/em><\/strong>C\u01a1 ch\u1ebf ASO c\u1eaft th\u00f4ng qua enzyme RNAse H v\u00e0 ASO c\u1ea3n tr\u1edf RNA<\/em><\/figcaption><\/figure>\n\n\n\n
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2.2. Small interfering RNA (siRNA)<\/strong><\/h3>\n\n\n\n

siRNA<\/strong> l\u00e0 c\u00e1c ph\u00e2n t\u1eed RNA kh\u00f4ng m\u00e3 h\u00f3a c\u00f3 c\u1ea5u tr\u00fac m\u1ea1ch \u0111\u00f4i, ng\u1eafn c\u00f3 vai tr\u00f2 \u0111\u1eb7c bi\u1ec7t trong vi\u1ec7c \u0111i\u1ec1u h\u00f2a gen v\u00e0 c\u0169ng r\u1ea5t \u0111\u1eb7c hi\u1ec7u v\u00ec ch\u00fang ch\u1ec9 ho\u1ea1t \u0111\u1ed9ng tr\u00ean m\u1ed9t m\u1ee5c ti\u00eau mRNA. C\u00e1c siRNA ch\u1ecbu tr\u00e1ch nhi\u1ec7m l\u00e0m im l\u1eb7ng gen \u1edf c\u1ea5p \u0111\u1ed9 sau phi\u00ean m\u00e3 b\u1eb1ng c\u00e1ch g\u00e2y ra s\u1ef1 can thi\u1ec7p RNA (RNAi). RNAi l\u00e0 m\u1ed9t qu\u00e1 tr\u00ecnh t\u1ef1 nhi\u00ean g\u00e2y ra s\u1ef1 im l\u1eb7ng c\u1ee7a gen th\u00f4ng qua s\u1ef1 ph\u00e2n h\u1ee7y mRNA. M\u1ed9t siRNA th\u00f4ng th\u01b0\u1eddng c\u00f3 chi\u1ec1u d\u00e0i t\u1eeb 19\u201321 nucleotide c\u00f9ng v\u1edbi hai nucleotide nh\u00f4 ra \u1edf \u0111\u1ea7u 3\u2019, ch\u1ee7 y\u1ebfu l\u00e0 TT v\u00e0 UU. C\u00e1c siRNA sau khi t\u1ed5ng h\u1ee3p th\u01b0\u1eddng \u0111\u01b0\u1ee3c b\u1ea3o v\u1ec7 v\u00e0 v\u1eadn chuy\u1ec3n b\u1eb1ng c\u00e1c h\u1ea1t nano \u0111\u1ec3 \u0111\u01b0a v\u00e0o t\u1ebf b\u00e0o. SiRNA sau khi nh\u1eadp b\u00e0o s\u1ebd ti\u1ebfn h\u00e0nh li\u00ean k\u1ebft v\u1edbi c\u00e1c ph\u1ea7n t\u1eed kh\u00e1c nh\u01b0 Ago \u0111\u1ec3 l\u1eafp r\u00e1p th\u00e0nh ph\u1ee9c h\u1ee3p RISC (RNA-induced silencing complex). C\u00e1c RISC sau khi \u0111\u01b0\u1ee3c l\u1eafp r\u00e1p s\u1ebd ph\u00e2n t\u00e1ch siRNA m\u1ea1ch \u0111\u00f4i th\u00e0nh m\u1ea1ch \u0111\u01a1n RNA, m\u1ea1ch \u0111\u01a1n n\u00e0y c\u00f3 kh\u1ea3 n\u0103ng \u0111\u1ecbnh h\u01b0\u1edbng li\u00ean k\u1ebft v\u1edbi mRNA m\u1ee5c ti\u00eau sau \u0111\u00f3 ph\u00e2n h\u1ee7y mRNA m\u1ee5c ti\u00eau \u0111\u00e3 li\u00ean k\u1ebft nh\u01b0 h\u00ecnh 3. T\u00ednh \u0111\u1ebfn th\u00e1ng 12 n\u0103m 2022 \u0111\u00e3 c\u00f3 5 lo\u1ea1i thu\u1ed1c siRNA \u0111\u01b0\u1ee3c FDA Hoa K\u1ef3 ph\u00ea duy\u1ec7t bao g\u1ed3m: Patisiran, Givosiran, Lumasiran, Inclisiran v\u00e0 Vutrisiran.<\/p>\n\n\n\n

\"H\u00ecnh
Figure 3. <\/strong>C\u1ea5u tr\u00fac v\u00e0 c\u01a1 ch\u1ebf ho\u1ea1t \u0111\u1ed9ng c\u1ee7a siRNA<\/em><\/figcaption><\/figure>\n\n\n\n
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2.3. MicroRNA (miRNA)<\/strong><\/h3>\n\n\n\n

miRNA <\/strong>l\u00e0 c\u00e1c tr\u00ecnh t\u1ef1 RNA kh\u00f4ng m\u00e3 h\u00f3a, ng\u1eafn \u0111i\u1ec1u ch\u1ec9nh bi\u1ec3u hi\u1ec7n gen b\u1eb1ng c\u00e1ch li\u00ean k\u1ebft v\u00e0 ph\u00e2n h\u1ee7y mRNA, \u1ee9c ch\u1ebf d\u1ecbch m\u00e3 ho\u1eb7c \u0111i\u1ec1u ch\u1ec9nh t\u00ednh \u1ed5n \u0111\u1ecbnh c\u1ee7a n\u00f3, c\u00f9ng nhi\u1ec1u t\u00e1c \u0111\u1ed9ng kh\u00e1c. miRNA l\u00e0 m\u1ed9t tr\u00ecnh t\u1ef1 RNA \u0111\u01a1n c\u00f3 chi\u1ec1u d\u00e0i t\u1eeb 21\u201325 nucleotide.<\/p>\n\n\n\n

C\u00e1c miRNA \u0111\u01b0\u1ee3c t\u1ea1o ra b\u1eaft \u0111\u1ea7u t\u1eeb qu\u00e1 tr\u00ecnh phi\u00ean m\u00e3 c\u1ee7a c\u00e1c miRNA gen d\u1ef1a tr\u00ean ho\u1ea1t \u0111\u1ed9ng c\u1ee7a enzyme RNA pol II t\u1eeb \u0111\u00f3 t\u1ea1o ra nh\u1eefng ph\u00e2n t\u1eed g\u1ecdi l\u00e0 primary \u2013 RNA (Pri-miRNA). C\u00e1c Pri-miR n\u00e0y sau \u0111\u00f3 b\u1ecb c\u1eaft b\u1edfi enzyme RNase-III-Drosha (trong nh\u00e2n) \u0111\u1ec3 t\u1ea1o th\u00e0nh c\u00e1c ph\u00e2n t\u1eed c\u00f3 c\u1ea5u tr\u00fac k\u1eb9p t\u00f3c g\u1ecdi l\u00e0 precursor-miRNA (pre-miR).  Sau khi \u0111\u01b0\u1ee3c v\u1eadn chuy\u1ec3n t\u1eeb nh\u00e2n ra ngo\u00e0i t\u1ebf b\u00e0o ch\u1ea5t d\u01b0\u1edbi t\u00e1c \u0111\u1ed9ng c\u1ee7a enzyme Dicer (ribonuclease III), c\u00e1c pre-miR n\u00e0y b\u1ecb c\u1eaft th\u00e0nh nh\u1eefng \u0111o\u1ea1n miR m\u1ea1ch \u0111\u00f4i (21-25 nts) . Ti\u1ebfp theo, ch\u1ec9 m\u1ed9t m\u1ea1ch miR k\u1ebft h\u1ee3p v\u1edbi c\u00e1c ph\u00e2n t\u1eed kh\u00e1c nh\u01b0 AGO2 \u0111\u1ec3 t\u1ea1o th\u00e0nh ph\u1ee9c h\u1ee3p RISC\/miR. Ph\u1ee9c h\u1ee3p RISC\/miR n\u00e0y sau \u0111\u00f3 li\u00ean k\u1ebft b\u1ed5 sung v\u1edbi mRNA \u0111\u00edch, d\u1eabn \u0111\u1ebfn \u1ee9c ch\u1ebf s\u1ef1 d\u1ecbch m\u00e3 (repression mRNA translation) ho\u1eb7c ph\u00e2n hu\u1ef7 c\u00e1c mRNA n\u00e0y (mRNA degradation), qua \u0111\u00f3 ki\u1ec3m so\u00e1t bi\u1ec3u hi\u1ec7n gen t\u01b0\u01a1ng \u1ee9ng.<\/p>\n\n\n\n

Nhi\u1ec1u nghi\u00ean c\u1ee9u \u0111\u00e3 ch\u1ee9ng minh miRNA tham gia v\u00e0 \u0111\u00f3ng m\u1ed9t vai tr\u00f2 quan tr\u1ecdng trong c\u00e1c qu\u00e1 tr\u00ecnh sinh l\u00fd v\u00e0 b\u1ec7nh l\u00fd c\u1ee7a c\u01a1 th\u1ec3 kh\u00e1c nhau nh\u01b0 ph\u00e2n chia t\u1ebf b\u00e0o, chu tr\u00ecnh ch\u1ebft t\u1ebf b\u00e0o, t\u1ea1o ra t\u1ebf b\u00e0o th\u1ea7n kinh, bi\u1ec7t h\u00f3a t\u1ea1o m\u00e1u v\u00e0 mi\u1ec5n d\u1ecbch. Ch\u00ednh v\u00ec v\u1eady, s\u1ef1 bi\u1ebfn \u0111\u1ed5i c\u1ee7a c\u00e1c miR, s\u1ef1 r\u1ed1i lo\u1ea1n ch\u1ee9c n\u0103ng c\u1ee7a qu\u00e1 tr\u00ecnh sinh t\u1ed5ng h\u1ee3p miR (miR biogenesis) ho\u1eb7c s\u1ef1 r\u1ed1i lo\u1ea1n bi\u1ec3u hi\u1ec7n c\u1ee7a miR c\u00f3 th\u1ec3 g\u00e2y ra nhi\u1ec1u lo\u1ea1i ung th\u01b0. Qua \u0111\u00f3, miR tr\u1edf th\u00e0nh m\u1ed9t d\u1ea5u \u1ea5n sinh h\u1ecdc ti\u1ec1m n\u0103ng trong c\u00e1c nghi\u00ean c\u1ee9u y sinh. Ngo\u00e0i ra miRNA c\u00f2n c\u00f3 c\u00e1c ti\u1ec1m n\u0103ng \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng trong c\u00e1c r\u1ed1i lo\u1ea1n kh\u00e1c ngo\u00e0i ung th\u01b0, nh\u01b0 trong c\u00e1c b\u1ec7nh v\u1ec1 r\u1ed1i lo\u1ea1n tho\u00e1i ho\u00e1 th\u1ea7n kinh.<\/p>\n\n\n\n

\"H\u00ecnh
Figure 4. <\/strong>Con \u0111\u01b0\u1eddng sinh t\u1ed5ng h\u1ee3p miRNA v\u00e0 c\u01a1 ch\u1ebf ph\u00e2n h\u1ee7y mRNA<\/em><\/figcaption><\/figure>\n\n\n\n
<\/div>\n\n\n\n

2.4. Aptamers<\/strong><\/h3>\n\n\n\n

Aptamer<\/strong> l\u00e0 c\u00e1c tr\u00ecnh t\u1ef1 oligonucleotide RNA ho\u1eb7c DNA \u0111\u01a1n ng\u1eafn th\u01b0\u1eddng c\u00f3 chi\u1ec1u d\u00e0i 20 \u0111\u1ebfn 60 nucleotide v\u00e0 c\u00f3 kh\u1ea3 n\u0103ng li\u00ean k\u1ebft c\u00e1c ph\u00e2n t\u1eed protein m\u1ee5c ti\u00eau b\u1eb1ng c\u00e1ch g\u1ea5p l\u1ea1i th\u00e0nh c\u1ea5u tr\u00fac ba chi\u1ec1u t\u01b0\u01a1ng t\u1ef1 nh\u01b0 kh\u00e1ng th\u1ec3, v\u1edbi \u0111\u1ed9 \u00e1i l\u1ef1c m\u1ea1nh v\u00e0 \u0111\u1ed9 \u0111\u1eb7c hi\u1ec7u cao.<\/p>\n\n\n\n

Hi\u1ec7n nay, m\u1ed9t s\u1ed1 l\u01b0\u1ee3ng l\u1edbn aptamer \u0111\u01b0\u1ee3c t\u1ea1o ra c\u00f3 th\u1ec3 li\u00ean k\u1ebft nhi\u1ec1u m\u1ee5c ti\u00eau kh\u00e1c nhau bao g\u1ed3m c\u00e1c ph\u00e2n t\u1eed v\u00f4 c\u01a1 \u0111\u01a1n gi\u1ea3n \u0111\u1ebfn c\u00e1c ph\u1ee9c h\u1ee3p protein l\u1edbn v\u00e0 to\u00e0n b\u1ed9 t\u1ebf b\u00e0o. Tr\u00ean th\u1ef1c t\u1ebf, aptamer th\u01b0\u1eddng \u0111\u01b0\u1ee3c g\u1ecdi l\u00e0 \u201ckh\u00e1ng th\u1ec3 h\u00f3a h\u1ecdc\u201d v\u00ec c\u00f3 ch\u1ee9c n\u0103ng t\u01b0\u01a1ng t\u1ef1 v\u1edbi kh\u00e1ng th\u1ec3 truy\u1ec1n th\u1ed1ng , nh\u01b0ng vi\u1ec7c t\u1ea1o ra aptamer d\u1ec5 d\u00e0ng h\u01a1n v\u00e0 r\u1ebb h\u01a1n \u0111\u00e1ng k\u1ec3 so v\u1edbi vi\u1ec7c s\u1ea3n xu\u1ea5t kh\u00e1ng th\u1ec3. H\u01a1n n\u1eefa, aptamer kh\u00f4ng g\u00e2y mi\u1ec5n d\u1ecbch c\u0169ng nh\u01b0 kh\u00f4ng \u0111\u1ed9c h\u1ea1i. T\u1ea5t c\u1ea3 nh\u1eefng \u0111\u1eb7c \u0111i\u1ec3m n\u00e0y l\u00e0m cho aptamer tr\u1edf th\u00e0nh \u1ee9ng c\u1eed vi\u00ean l\u00fd t\u01b0\u1edfng cho c\u00e1c \u1ee9ng d\u1ee5ng ch\u1ea9n \u0111o\u00e1n v\u00e0 \u0111i\u1ec1u tr\u1ecb, tinh ch\u1ebf c\u00e1c ph\u00e2n t\u1eed m\u1ee5c ti\u00eau t\u1eeb c\u00e1c h\u1ed7n h\u1ee3p ph\u1ee9c t\u1ea1p, thi\u1ebft k\u1ebf c\u1ea3m bi\u1ebfn sinh h\u1ecdc (biosensor), v.v. Aptamer \u0111\u01b0\u1ee3c \u00e1p d\u1ee5ng r\u1ed9ng r\u00e3i \u0111\u1ebfn m\u1ee9c c\u00e1c b\u00e1o c\u00e1o m\u1edbi li\u00ean quan \u0111\u1ebfn aptamer \u0111\u01b0\u1ee3c c\u00f4ng b\u1ed1 g\u1ea7n nh\u01b0 m\u1ed7i ng\u00e0y.<\/p>\n\n\n\n

M\u1ed9t c\u01a1 s\u1edf d\u1eef li\u1ec7u \u0111\u1eb7c bi\u1ec7t \u0111\u00e3 \u0111\u01b0\u1ee3c t\u1ea1o (http:\/\/aptamer.icmb.utexas.edu) \u0111\u1ec3 ph\u00e2n lo\u1ea1i d\u1eef li\u1ec7u li\u00ean quan \u0111\u1ebfn aptamer v\u00e0 cung c\u1ea5p quy\u1ec1n truy c\u1eadp v\u00e0o th\u00f4ng tin v\u1ec1 nhi\u1ec1u aptamer hi\u1ec7n c\u00f3. Aptamer th\u01b0\u1eddng \u0111\u01b0\u1ee3c ph\u00e2n l\u1eadp b\u1eb1ng m\u1ed9t ph\u01b0\u01a1ng ph\u00e1p \u0111\u01b0\u1ee3c g\u1ecdi Systematic Evolution of Ligands by EXponential enrichment (SELEX), \u0111\u01b0\u1ee3c m\u00f4 t\u1ea3 l\u1ea7n \u0111\u1ea7u ti\u00ean c\u00e1ch \u0111\u00e2y 25 n\u0103m. Aptamer \u0111\u1ea7u ti\u00ean \u0111\u01b0\u1ee3c ph\u00ea duy\u1ec7t cho \u1ee9ng d\u1ee5ng \u0111i\u1ec1u tr\u1ecb l\u00e0 pegaptanib natri (Macugen; Pfizer\/Eyetech), \u0111\u01b0\u1ee3c C\u1ee5c Qu\u1ea3n l\u00fd Th\u1ef1c ph\u1ea9m v\u00e0 D\u01b0\u1ee3c ph\u1ea9m Hoa K\u1ef3 ph\u00ea duy\u1ec7t v\u00e0o n\u0103m 2004 \u0111\u1ec3 \u0111i\u1ec1u tr\u1ecb tho\u00e1i h\u00f3a \u0111i\u1ec3m v\u00e0ng v\u00e0 8 aptamer kh\u00e1c hi\u1ec7n \u0111ang \u0111\u01b0\u1ee3c \u0111\u00e1nh gi\u00e1 l\u00e2m s\u00e0ng v\u1ec1 c\u00e1c ch\u1ec9 \u0111\u1ecbnh v\u1ec1 huy\u1ebft h\u1ecdc, ung th\u01b0, m\u1eaft v\u00e0 vi\u00eam kh\u00e1c nhau.<\/p>\n\n\n\n

\"H\u00ecnh
Figure 5. <\/strong>C\u1ea5u tr\u00fac c\u1ee7a Aptamer v\u00e0 kh\u00e1ng th\u1ec3 khi li\u00ean k\u1ebft v\u1edbi protein<\/em><\/figcaption><\/figure>\n\n\n\n
<\/div>\n\n\n\n

3. C\u00e1c \u1ee9ng d\u1ee5ng ti\u1ec1m n\u0103ng c\u1ee7a Oligonucleotide tr\u1ecb li\u1ec7u<\/strong><\/h2>\n\n\n\n

C\u00e1c oligonucleotide tr\u1ecb li\u1ec7u c\u00f3 ph\u1ea1m vi \u1ee9ng d\u1ee5ng r\u1ed9ng r\u00e3i, t\u1eeb c\u00e1c b\u1ec7nh di truy\u1ec1n th\u00f4ng th\u01b0\u1eddng \u0111\u1ebfn c\u00e1c b\u1ec7nh hi\u1ebfm g\u1eb7p. M\u1ed9t s\u1ed1 \u1ee9ng d\u1ee5ng n\u1ed5i b\u1eadt nh\u1ea5t bao g\u1ed3m:<\/p>\n\n\n\n

B\u1ec7nh di truy\u1ec1n:<\/strong> oligonucleotide c\u00f3 th\u1ec3 \u0111i\u1ec1u ch\u1ec9nh \u0111\u1eb7c hi\u1ec7u v\u1edbi c\u00e1c \u0111\u1ed9t bi\u1ebfn gen g\u00e2y ra c\u00e1c b\u1ec7nh nh\u01b0 lo\u1ea1n d\u01b0\u1ee1ng c\u01a1 Duchenne, teo c\u01a1 c\u1ed9t s\u1ed1ng v\u00e0 x\u01a1 nang.<\/p>\n\n\n\n

Ung th\u01b0:<\/strong> C\u00e1c oligonucleotide c\u00f3 th\u1ec3 nh\u1eafm m\u1ee5c ti\u00eau v\u00e0o c\u00e1c gen li\u00ean quan \u0111\u1ebfn s\u1ef1 t\u0103ng sinh v\u00e0 s\u1ed1ng s\u00f3t c\u1ee7a t\u1ebf b\u00e0o, \u0111\u00e2y l\u00e0 m\u1ed9t ph\u01b0\u01a1ng ph\u00e1p tr\u1ecb li\u1ec7u m\u1edbi trong cu\u1ed9c chi\u1ebfn ch\u1ed1ng l\u1ea1i ung th\u01b0.<\/p>\n\n\n\n

B\u1ec7nh tho\u00e1i h\u00f3a th\u1ea7n kinh:<\/strong> Oligonucleotide c\u00f3 th\u1ec3 \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng \u0111\u1ec3 \u0111i\u1ec1u ch\u1ec9nh bi\u1ec3u hi\u1ec7n gen trong c\u00e1c b\u1ec7nh nh\u01b0 h\u1ed9i ch\u1ee9ng Huntington v\u00e0 b\u1ec7nh x\u01a1 c\u1ee9ng teo c\u01a1 m\u1ed9t b\u00ean (ALS).<\/p>\n\n\n\n

B\u1ec7nh chuy\u1ec3n h\u00f3a:<\/strong> Ch\u00fang c\u00f3 th\u1ec3 \u0111i\u1ec1u ch\u1ec9nh c\u00e1c gen li\u00ean quan \u0111\u1ebfn c\u00e1c b\u1ec7nh chuy\u1ec3n h\u00f3a, ch\u1eb3ng h\u1ea1n nh\u01b0 t\u0103ng cholesterol m\u00e1u mang t\u00ednh ch\u1ea5t di truy\u1ec1n.<\/p>\n\n\n\n

<\/div>\n\n\n\n

T\u00e0i li\u1ec7u tham kh\u1ea3o<\/strong><\/h2>\n\n\n\n
    \n
  1. Anthony, K. (2022). RNA-based therapeutics for neurological diseases. <\/a>RNA biology, 19(1), 176-190.<\/li>\n\n\n\n
  2. Aptamers. (n.d.). Lubio.Ch. Retrieved June 11, 2024, from https:\/\/www.lubio.ch\/blog\/aptamers<\/li>\n\n\n\n
  3. Collotta, D., Bertocchi, I., Chiapello, E., & Collino, M. (2023). Antisense oligonucleotides: a novel Frontier in pharmacological strategy.<\/a> Frontiers in Pharmacology, 14, 1304342.<\/li>\n\n\n\n
  4. Crooke, S. T., Liang, X. H., Baker, B. F., & Crooke, R. M. (2021). Antisense technology: A review. Journal of Biological Chemistry, 296.<\/a><\/li>\n\n\n\n
  5. Dhuri, K., Bechtold, C., Quijano, E., Pham, H., Gupta, A., Vikram, A., & Bahal, R. (2020). Antisense oligonucleotides: an emerging area in drug discovery and development. <\/a>Journal of clinical medicine, 9(6), 2004.<\/li>\n\n\n\n
  6. Haque, U. S., & Yokota, T. (2023). Enhancing Antisense Oligonucleotide-Based Therapeutic Delivery with DG9, a Versatile Cell-Penetrating Peptide. Cells, 12(19), 2395.<\/li>\n\n\n\n
  7. Introduction to therapeutic oligonucleotides: Transforming medicine from genetics. (n.d.). Oligofastx.com. Retrieved June 11, 2024, from https:\/\/oligofastx.com\/introduction-to-therapeutic-oligonucleotides-transforming-medicine-from-genetics\/<\/li>\n\n\n\n
  8. Jiang, L., Qi, Y., Yang, L., Miao, Y. B., Ren, W., Liu, H., … & Cai, L. (2023). Remodeling the tumor immune microenvironment via siRNA therapy for precision cancer treatment. Asian Journal of Pharmaceutical Sciences, 100852.<\/li>\n\n\n\n
  9. Keefe, A. D., Pai, S., & Ellington, A. (2010). Aptamers as therapeutics. Nature reviews Drug discovery, 9(7), 537-550.<\/li>\n\n\n\n
  10. Oligonucleotide therapy development around the world. (2018, February 14). Atelocollagen.com; Koken Co., Ltd. https:\/\/atelocollagen.com\/en\/information\/info180214<\/li>\n\n\n\n
  11. Papaioannou, I., Owen, J. S., & Y\u00e1\u00f1ez\u2010Mu\u00f1oz, R. J. (2023). Clinical applications of gene therapy for rare diseases: A review. International Journal of Experimental Pathology, 104(4), 154-176.<\/li>\n\n\n\n
  12. Ranasinghe, P., Addison, M. L., Dear, J. W., & Webb, D. J. (2023). Small interfering RNA: Discovery, pharmacology and clinical development\u2014An introductory review. British Journal of Pharmacology, 180(21), 2697-2720.<\/li>\n<\/ol>","protected":false},"excerpt":{"rendered":"

    Oligonucleotide tr\u1ecb li\u1ec7u \u0111ang \u0111\u01b0\u1ee3c quan t\u00e2m v\u1edbi nhi\u1ec1u ti\u1ec1m n\u0103ng cung c\u1ea5p c\u00e1c ph\u01b0\u01a1ng ph\u00e1p \u0111i\u1ec1u tr\u1ecb cho c\u00e1c b\u1ec7nh di truy\u1ec1n v\u00e0\/ho\u1eb7c c\u00e1c b\u1ec7nh hi\u1ebfm g\u1eb7p. Nh\u1eefng tr\u00ecnh t\u1ef1 oligonucleotide DNA ho\u1eb7c RNA n\u00e0y \u0111\u00e3 c\u00e1ch m\u1ea1ng h\u00f3a l\u0129nh v\u1ef1c y h\u1ecdc hi\u1ec7n \u0111\u1ea1i. B\u00e0i vi\u1ebft n\u00e0y s\u1ebd cung c\u1ea5p nh\u1eefng th\u00f4ng tin xoay quanh oligonucleotide tr\u1ecb li\u1ec7u, c\u00e1ch ch\u00fang ho\u1ea1t \u0111\u1ed9ng v\u00e0 c\u00e1c \u1ee9ng d\u1ee5ng ti\u1ec1m n\u0103ng c\u1ee7a ch\u00fang, \u0111\u1eb7c bi\u1ec7t t\u1eadp trung v\u00e0o s\u1ef1 \u0111\u00f3ng g\u00f3p c\u1ee7a oligonucleotide trong vi\u1ec7c ph\u00e1t tri\u1ec3n c\u00e1c li\u1ec7u ph\u00e1p \u0111i\u1ec1u tr\u1ecb v\u00e0 chu\u1ea9n \u0111o\u00e1n.<\/p>","protected":false},"author":1,"featured_media":11484,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_uag_custom_page_level_css":"","site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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Team","author_link":"https:\/\/abtvn.com\/en\/author\/admin\/"},"uagb_comment_info":0,"uagb_excerpt":"Oligonucleotide tr\u1ecb li\u1ec7u \u0111ang \u0111\u01b0\u1ee3c quan t\u00e2m v\u1edbi nhi\u1ec1u ti\u1ec1m n\u0103ng cung c\u1ea5p c\u00e1c ph\u01b0\u01a1ng ph\u00e1p \u0111i\u1ec1u tr\u1ecb cho c\u00e1c b\u1ec7nh di truy\u1ec1n v\u00e0\/ho\u1eb7c c\u00e1c b\u1ec7nh hi\u1ebfm g\u1eb7p. Nh\u1eefng tr\u00ecnh t\u1ef1 oligonucleotide DNA ho\u1eb7c RNA n\u00e0y \u0111\u00e3 c\u00e1ch m\u1ea1ng h\u00f3a l\u0129nh v\u1ef1c y h\u1ecdc hi\u1ec7n \u0111\u1ea1i. B\u00e0i vi\u1ebft n\u00e0y s\u1ebd cung c\u1ea5p nh\u1eefng th\u00f4ng tin…","_links":{"self":[{"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/posts\/11467","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/comments?post=11467"}],"version-history":[{"count":6,"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/posts\/11467\/revisions"}],"predecessor-version":[{"id":13073,"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/posts\/11467\/revisions\/13073"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/media\/11484"}],"wp:attachment":[{"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/media?parent=11467"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/categories?post=11467"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/abtvn.com\/en\/wp-json\/wp\/v2\/tags?post=11467"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}