https://news.mit.edu/2024/charmed-collaboration-creates-therapy-candidate-fatal-prion-diseases-0627

CHARMed collaboration creates a potent therapy candidate for fatal prion diseasesMIT Whitehead and Broad Institute researchers designed an epigenetic editor that can silence the prion protein gene, which could potentially be developed into a therapy against fatal prion diseases. The same approach could be used against other genetic diseases.news.mit.edu

https://www.nature.com/articles/d41586-024-02115-z

โ€˜Epigenome editorโ€™ silences gene that causes deadly brain disordersPrion diseases are caused by misfolded proteins, but a new tool can stop them forming in mice.www.nature.com


That is why Vallabh was excited to discover, when she entered into a collaboration with Whitehead Institute for Biomedical Research member Jonathan Weissman, that Weissmanโ€™s group likes to work at full throttle. In less than two years, Weissman, Vallabh, and their collaborators have developed a set of molecular tools called CHARMs that can turn off disease-causing genes such as the prion protein gene โ€” as well as, potentially, genes coding for many other proteins implicated in neurodegenerative and other diseases โ€” and they are refining those tools to be good candidates for use in human patients. Although the tools still have many hurdles to pass before the researchers will know if they work as therapeutics, the team is encouraged by the speed with which they have developed the technology thus far.

โ€œThe spirit of the collaboration since the beginning has been that there was no waiting on formality,โ€ Vallabh says. โ€œAs soon as we realized our mutual excitement to do this, everything was off to the races.โ€



๋จผ์ € ํ”„๋ฆฌ์˜จ ์ฒจ๋“ฃ๋Š” ๊ฒŒ์ด๋“ค์„ ์œ„ํ•ด ๊ฐ„๋‹จํžˆ ์„ค๋ช…ํ•จ.ย ์š”์•ฝํ•˜๋ฉด ๋‡Œ๋ฅผ ๊ฐœ๋ฐ•์‚ด๋‚ด๋Š” ๋…์„ฑ ๋‹จ๋ฐฑ์งˆ์ธ๋ฐ ์–˜๊ฐ€ ์ผ์œผํ‚ค๋Š” ๋Œ€ํ‘œ์ ์ธ ๋ณ‘์ด ๊ด‘์šฐ๋ณ‘, ๊ด‘๋ก๋ณ‘, ์Šคํฌ๋ž˜ํ”ผ, ์•ผ์ฝฅ๋ณ‘์ž„. ์น˜๋ฃŒ๋ฒ•์€ ์ปค๋…• ์˜ˆ๋ฐฉ๋ฒ•๋„ ์ „๋ฌดํ•˜๊ณ  ๋‡Œ๋งŒย ์ง‘์ค‘์ ์œผ๋กœ ์กฐ์ง€๋Š” ์ƒˆ๋ผ๋ผ ๊ฑธ๋ฆฌ๋ฉด ์น˜์‚ฌ์œจ 100ํผ์—(๊ด‘๊ฒฌ๋ณ‘ ๊ฐ™์€ ์‚ฌ์‹ค์ƒ 100ํผ๋„ ์•„๋‹ˆ๊ณ  ๋ฌธ์ž ๊ทธ๋Œ€๋กœ 100ํผ)ย ๊ณฑ๊ฒŒ ์ฃฝ๋Š” ๊ฒƒ๋„ ์•„๋‹ˆ๊ณ  ์น˜๋งค ๊ฑธ๋ ค์„œ ๋˜ฅ์˜ค์คŒ ํฉ๋ฟŒ๋ฆฌ๋‹ค๊ฐ€ ๋น„์ฐธํ•˜๊ฒŒ ๋’ค์ง„๋‹ค

๋ฒˆ์—ญํ•˜๊ธฐ ๊ท€์ฐฎ์•„์„œ ๊ฐ„๋‹จํžˆ ์š”์•ฝํ•˜์ž๋ฉด ๊ทธ๋™์•ˆ ์ธ๋ฅ˜๊ฐ€ ์† ์“ธ ๋ฐฉ๋„๊ฐ€ ์—†์–ด์„œ ๋ถˆ, ๋ฝ์Šค, ์˜คํ† ํด๋ ˆ์ด๋ธŒ๋กœ ๋ฐ–์— ๋ชป ์—†์• ๋˜ ๋ณ‘์›์ฒด์ธ ํ”„๋ฆฌ์˜จ์„ ํฌ๋ฆฌ์Šคํผ๋ฅผ ๊ฐœ์กฐํ•œ ์œ ์ „์ž๊ฐ€์œ„๋กœ ์นจ๋ฌต์‹œ์ผฐ์Œ

์ฅ๋ฅผ ๋Œ€์ƒ์œผ๋กœ ์‹คํ—˜ํ•œ ๊ฒฐ๊ณผ ํ”„๋ฆฌ์˜จ ๋ฐœํ˜„ ์†๋„๋ฅผ 80% ๋Šฆ์ท„๋Š”๋ฐ ์ด๋Š” ํ”„๋ฆฌ์˜จ ์น˜๋ฃŒ์— ํ•„์š”ํ•œ ์ˆ˜์น˜๋ณด๋‹ค ํ›จ์”ฌ ๋†’์€ ์ˆ˜์น˜์ž„. ์ด์ „ ์‹คํ—˜์— ๋”ฐ๋ฅด๋ฉด ํ”„๋ฆฌ์˜จ์˜ 20%๋งŒ ์นจ๋ฌต์‹œ์ผœ๋„ ์ฆ์ƒ์ด ๊ฐœ์„ ๋œ๋‹ค๊ณ  ํ•จ

์ฐธ๊ณ ๋กœ ํ”„๋ฆฌ์˜จ ๋ฟ ์•„๋‹ˆ๋ผ ์•Œ์ธ ํ•˜์ด๋จธ ๋“ฑ์„ ์ผ์œผํ‚ค๋Š” ๋…์„ฑ ๋‹จ๋ฐฑ์งˆ๋„ ์นจ๋ฌต์‹œํ‚ฌ ๊ฐ€๋Šฅ์„ฑ๋„ ์žˆ๋‹ค๊ณ ๋„ ์–ธ๊ธ‰ํ–ˆ์Œ

์•„์ง์€ ์ฅ ์‹คํ—˜ ๋‹จ๊ณ„์ด๊ณ  ์œ ์ „์ž๊ฐ€์œ„ ํŠน์„ฑ์ƒ ์ž„์ƒ ์„ฑ๊ณตํ•ด๋„ ์˜ค์งˆ๋‚˜๊ฒŒ ๋น„์Œ€ํ…Œ์ง€๋งŒ ๊ทธ๋™์•ˆ ํ”„๋ฆฌ์˜จ ๋ณ€ํ˜•์„ ์นจ๋ฌต์‹œํ‚ค๊ธด ์ปค๋…• ๋ชฉ์ˆจ์ค„๋งŒ ๊ฒจ์šฐ ์—ฐ์žฅํ•  ์ˆ˜ ์žˆ์—ˆ๋˜ ๊ฑธ ์ƒ๊ฐํ•˜๋ฉด ๋ฌด์ง€๋ง‰์ง€ํ•˜๊ฒŒ ๋ฐœ์ „ํ•œ๊ฑฐ์ž„






๊ทธ๋Ÿฐ๋ฐ ์ข†๊ฐ„์€ ํ”„๋ฆฌ์˜จ๋„ ์—†์•จ ์ˆ˜ ์žˆ์œผ๋ฉด์„œ ์™œ m์ž ํƒˆ๋ชจ์—” ์† ๋ชป ๋Œ€๋Š”๊ฑฐ๋…ธ?