Antisense Oligonucleotide (ASO)
2025. 4. 25. 15:23
๋ฐ˜์‘ํ˜•

๐Ÿงฌ Antisense Oligonucleotide (ASO)

๐Ÿ’ก ๊ฐœ๋…

  • ASO๋Š” ์งง์€ ๋‹จ์ผ๊ฐ€๋‹ฅ DNA ๋˜๋Š” RNA ์„œ์—ด๋กœ, ํ‘œ์  mRNA์™€ ์ƒ๋ณด์ ์œผ๋กœ ๊ฒฐํ•ฉํ•˜์—ฌ ์œ ์ „์ž ๋ฐœํ˜„์„ ์กฐ์ ˆํ•˜๋Š” ์น˜๋ฃŒ์ œ.
  • ๊ธฐ๋Šฅ: ์œ ์ „์ž ์–ต์ œ(silencing), ์Šคํ”Œ๋ผ์ด์‹ฑ ์กฐ์ ˆ ๋“ฑ

๐Ÿงช ์ž‘์šฉ ๊ธฐ์ „

๊ธฐ์ „ ์œ ํ˜• ์„ค๋ช…

๐Ÿ”น RNase H ํ™œ์„ฑํ™” ASO๊ฐ€ mRNA์— ๊ฒฐํ•ฉ → RNase H๊ฐ€ mRNA ๋ถ„ํ•ด → ๋‹จ๋ฐฑ์งˆ ์ƒ์„ฑ ์–ต์ œ
๐Ÿ”น ์Šคํ”Œ๋ผ์ด์‹ฑ ์กฐ์ ˆ ์ „์‚ฌ์ฒด์˜ ์Šคํ”Œ๋ผ์ด์‹ฑ ํŒจํ„ด ๋ณ€ํ™” → ๋น„์ •์ƒ ๋‹จ๋ฐฑ์งˆ ์ƒ์„ฑ ์–ต์ œ or ๊ธฐ๋Šฅ ํšŒ๋ณต
๐Ÿ”น ๋ฒˆ์—ญ ์ฐจ๋‹จ ๋ฆฌ๋ณด์†œ์˜ ์ ‘๊ทผ์„ ๋ง‰์•„ ๋‹จ๋ฐฑ์งˆ ํ•ฉ์„ฑ ์–ต์ œ

๐Ÿ’Š ์ฃผ์š” ์ ์‘์ฆ

๋ถ„์•ผ ์ ์šฉ ์งˆํ™˜

์œ ์ „์งˆํ™˜ Spinal Muscular Atrophy (SMA), Duchenne Muscular Dystrophy (DMD)
์•” BCL2 ์–ต์ œ ๋“ฑ ํŠน์ • ์ข…์–‘ ์œ ์ „์ž ํƒ€๊ฒŸ
๋ฐ”์ด๋Ÿฌ์Šค ์งˆํ™˜ HIV, HBV ๋“ฑ ๋ฐ”์ด๋Ÿฌ์Šค ๋ณต์ œ ์–ต์ œ ์‹œ๋„

๐Ÿ” ๋Œ€ํ‘œ ์•ฝ๋ฌผ

์•ฝ๋ฌผ๋ช… ์ ์‘์ฆ ๊ธฐ์ „

Nusinersen (Spinraza) SMA ์Šคํ”Œ๋ผ์ด์‹ฑ ์กฐ์ ˆ
Eteplirsen DMD exon skipping
Inotersen (Tegsedi) hATTR (์œ ์ „์„ฑ ์•„๋ฐ€๋กœ์ด๋“œ์ฆ) RNase H ๊ธฐ์ „

โš™๏ธ ํŠน์ง• ๋ฐ ํ•œ๊ณ„

์žฅ์  ๋‹จ์ 

๐ŸŽฏ ๋†’์€ ํŠน์ด์„ฑ ๐Ÿ” ๋ฐ˜๋ณต ํˆฌ์—ฌ ํ•„์š” (์งง์€ ๋ฐ˜๊ฐ๊ธฐ)
๐Ÿ”ฌ ์œ ์ „์ž ์ˆ˜์ค€ ํƒ€๊ฒŸํŒ… ๊ฐ€๋Šฅ ๐Ÿšซ ์กฐ์ง ์นจํˆฌ์„ฑ ๋‚ฎ์Œ (ํŠนํžˆ CNS)
๐Ÿ’ก ์Šคํ”Œ๋ผ์ด์‹ฑ ๋“ฑ ์ •๋ฐ€์กฐ์ ˆ ๊ฐ€๋Šฅ ๐Ÿ’ธ ๋†’์€ ๊ฐœ๋ฐœ ๋น„์šฉ ๋ฐ ์ œํ˜• ๋ฌธ์ œ

๐Ÿ“š ์ฐธ๊ณ  ์ถœ์ฒ˜

  • Bennett CF. Antisense oligonucleotide therapies. Annu Rev Pharmacol Toxicol. 2017.
  • Crooke ST. Molecular mechanisms of antisense oligonucleotides. Nucleic Acid Ther. 2017.
  • FDA Drug Database (Spinraza, Tegsedi, Exondys 51 ๋“ฑ)
  • Nature Reviews Drug Discovery (2022), "Next-generation antisense platforms"
๋ฐ˜์‘ํ˜•