иҝ‘ж—ҘпјҢдёҠжө·з§‘жҠҖеӨ§еӯҰз”ҹе‘Ҫ科еӯҰдёҺжҠҖжңҜеӯҰйҷўйҷҲдҪіиҜҫйўҳз»„дёҺеҗҲдҪңиҖ…й’ҲеҜ№еҸҳеҪўејҸзўұеҹәзј–иҫ‘еҷЁпјҲtransformer base editor, tBEпјүеңЁдёҚеҗҢйҒ—дј иғҢжҷҜдёӢдёҙеәҠжІ»з–—ОІ-иЎҖзәўиӣӢзҷҪз—…зҡ„研究еҸ–еҫ—йҮҚиҰҒиҝӣеұ•гҖӮеҗҲдҪңеӣўйҳҹеҹәдәҺиҮӘдё»ејҖеҸ‘зҡ„tBEеҸ‘еұ•зҡ„зўұеҹәзј–иҫ‘з–—жі•жҲҗеҠҹеә”з”ЁдәҺжІ»з–—й•°еҲҖеһӢз»Ҷиғһиҙ«иЎҖз—…пјҲSCDпјүжӮЈиҖ…д»ҘеҸҠжқҘиҮӘдёңеҚ—дәҡе’ҢеҚ—дәҡзҡ„ОІ-ең°дёӯжө·иҙ«иЎҖпјҲTDTпјүжӮЈиҖ…пјҢе®һзҺ°дәҶжҢҒз»ӯзЁіе®ҡзҡ„й«ҳж•Ҳзј–иҫ‘пјҢзЎ®дҝқдәҶдёҙеәҠжІ»з–—зҡ„жңүж•ҲжҖ§е’Ңе®үе…ЁжҖ§гҖӮзӣёе…іжҲҗжһңд»ҘвҖңClinical base editing for ОІ-hemoglobinopathies across different genetic backgroundsвҖқдёәйўҳпјҢеңЁеӣҪйҷ…еӯҰжңҜжңҹеҲҠгҖҠз»ҶиғһВ·е№Із»ҶиғһгҖӢпјҲCell Stem CellпјүдёҠеҸ‘иЎЁгҖӮ

еӣҫ1 | зўұеҹәзј–иҫ‘жҠҖжңҜtBEеңЁдёҚеҗҢйҒ—дј иғҢжҷҜдёӢеҜ№ОІ-иЎҖзәўиӣӢзҷҪз—…зҡ„дёҙеәҠеә”用研究жҰӮи§Ҳ

ОІ-иЎҖзәўиӣӢзҷҪз—…жҳҜдё–з•ҢдёҠжңҖеёёи§Ғзҡ„еҚ•еҹәеӣ йҒ—дј з—…д№ӢдёҖпјҢй•°зҠ¶еҲҖеһӢз»Ҷиғһиҙ«иЎҖз—…жҜҸе№ҙеҪұе“Қи¶…иҝҮ30дёҮеҗҚж–°з”ҹе„ҝпјҢОІ-ең°дёӯжө·иҙ«иЎҖжҜҸе№ҙеҪұе“Қи¶…иҝҮ4дёҮеҗҚж–°з”ҹе„ҝгҖӮдј з»ҹCRISPR-Cas9ж ёй…ёй…¶жҠҖжңҜйҖҡиҝҮиҜұеҜјDNAеҸҢй“ҫж–ӯиЈӮе®һзҺ°еҹәеӣ зј–иҫ‘пјҢиҷҪ然已еңЁдёҙеәҠдёӯеҸ–еҫ—дёҖе®ҡз–—ж•ҲпјҢдҪҶеҸҢй“ҫж–ӯиЈӮеҸҜиғҪеј•еҸ‘p53дҫқиө–жҖ§DNAжҚҹдјӨеҸҚеә”гҖҒйҖ иЎҖе№Із»ҶиғһйҖӮеә”жҖ§еҸ—жҚҹеҸҠеӨ§зүҮж®өжҹ“иүІдҪ“зјәеӨұзӯүйЈҺйҷ©гҖӮзўұеҹәзј–иҫ‘жҠҖжңҜиғҪеӨҹеңЁдёҚз ҙеқҸDNAеҸҢй“ҫзҡ„жғ…еҶөдёӢе®һзҺ°еҚ•дёӘзўұеҹәзҡ„зІҫеҮҶиҪ¬жҚўпјҢдёәиҝҷдёҖеӣ°еўғжҸҗдҫӣдәҶе…Ёж–°зҡ„и§ЈеҶіж–№жЎҲгҖӮ

еӣўйҳҹеҲ©з”ЁеүҚжңҹејҖеҸ‘зҡ„еҸҳеҪўејҸзўұеҹәзј–иҫ‘еҷЁпјҲtBEпјүвҖ”вҖ”дёҖз§ҚйҖҡиҝҮи„ұж°§иғһиӢ·и„ұж°Ёй…¶жҠ‘еҲ¶иӣӢзҷҪи®ҫи®Ўд»ҘжңҖеӨ§йҷҗеәҰеҮҸе°‘и„ұйқ¶зӘҒеҸҳзҡ„й«ҳзІҫеәҰиғһеҳ§е•¶зўұеҹәзј–иҫ‘еҷЁвҖ”вҖ”йқ¶еҗ‘з ҙеқҸHBG1/2еҗҜеҠЁеӯҗеҶ…BCL11Aзҡ„з»“еҗҲеҹәеәҸпјҢд»ҺиҖҢеҶҚжҝҖжҙ»HbFиЎЁиҫҫгҖӮеңЁжӯӨеүҚ研究дёӯпјҢдә”еҗҚдёӯеӣҪTDTжӮЈиҖ…еңЁжҺҘеҸ—tBEд»ӢеҜјзҡ„зўұеҹәзј–иҫ‘з–—жі•еҗҺе·Із»Ҹе…ЁйғЁе®һзҺ°е®Ңе…Ёж‘Ҷи„ұиҫ“иЎҖдҫқиө–зҡ„зӣ®ж ҮгҖӮ

жң¬е·ҘдҪңиҝӣдёҖжӯҘе°ҶtBEе№іеҸ°зҡ„еә”з”Ёжү©еұ•иҮідёҚеҗҢйҒ—дј иғҢжҷҜзҡ„жӮЈиҖ…зҫӨдҪ“пјҢеҢ…жӢ¬дёҖеҗҚжқҘиҮӘе°јж—ҘеҲ©дәҡзҡ„SCDжӮЈиҖ…пјҲжӮЈиҖ…1пјҢОІ^S/ОІ^Sпјүд»ҘеҸҠдёүеҗҚеҲҶеҲ«жқҘиҮӘиҖҒжҢқпјҲжӮЈиҖ…2пјҢОІ^вҒ°/ОІ^бҙұпјүгҖҒ马жқҘиҘҝдәҡпјҲжӮЈиҖ…3пјҢиҸІеҫӢе®ҫеһӢзјәеӨұпјҢОІ^вҒ°/ОІ^вҒ°пјүе’Ңе·ҙеҹәж–ҜеқҰпјҲжӮЈиҖ…4пјҢеҚ•ж ёиӢ·й…ёжҸ’е…ҘпјҢОІ^вҒ°/ОІ^вҒ°пјүзҡ„TDTжӮЈиҖ…пјҢд»ҘиҜ„дј°tBEд»ӢеҜјзҡ„зўұеҹәзј–иҫ‘з–—жі•еңЁйҒ—дј еӨҡж ·жҖ§ОІ-иЎҖзәўиӣӢзҷҪз—…дәәзҫӨдёӯзҡ„жІ»з–—йҖӮз”ЁжҖ§гҖӮ

дёҙеәҠж•°жҚ®жҳҫзӨәпјҢжүҖжңүжӮЈиҖ…еңЁжҺҘеҸ—еҚ•ж¬ЎtBEзј–иҫ‘иҮӘдҪ“йҖ иЎҖе№Із»Ҷиғһиҫ“жіЁеҗҺпјҢеқҮе®һзҺ°дәҶеҝ«йҖҹйҖ иЎҖйҮҚе»әпјҢ并еңЁжІ»з–—еҗҺзҹӯжңҹеҶ…е®Ңе…Ёж‘Ҷи„ұиҫ“иЎҖдҫқиө–гҖӮз»ҸиҝҮ12дёӘжңҲд»ҘдёҠзҡ„йҡҸи®ҝпјҢжӮЈиҖ…еңЁйӘЁй«“е’ҢеӨ–е‘ЁиЎҖдёӯеқҮиЎЁзҺ°еҮәзЁіе®ҡжҢҒд№…зҡ„зўұеҹәзј–иҫ‘ж•ҲзҺҮгҖҒжҢҒз»ӯй«ҳж°ҙе№ізҡ„HbFиЎЁиҫҫд»ҘеҸҠе®Ңе…Ёж‘Ҷи„ұиҫ“иЎҖдҫқиө–гҖӮSCDжӮЈиҖ…еңЁйҡҸи®ҝжңҹй—ҙжңӘеҮәзҺ°иЎҖз®Ўй—ӯеЎһеҚұиұЎпјҲVOCsпјҢvaso-occlusive crisesпјүгҖӮе®үе…ЁжҖ§ж–№йқўпјҢжңӘжЈҖжөӢеҲ°и„ұйқ¶зӘҒеҸҳпјҢжңӘеҮәзҺ°дә§е“Ғзӣёе…ізҡ„дёҚиүҜдәӢ件гҖӮ

еңЁSCDжӮЈиҖ…дёӯпјҢдёӯжҖ§зІ’з»Ҷиғһе’ҢиЎҖе°ҸжқҝеҲҶеҲ«дәҺиҫ“жіЁеҗҺ第13еӨ©е’Ң第21еӨ©жҲҗеҠҹжӨҚе…ҘпјӣжҖ»иЎҖзәўиӣӢзҷҪд»Һеҹәзәҝзҡ„7.7 g/dLеҚҮиҮіз¬¬3дёӘжңҲзҡ„12.9 g/dLпјҢ并жҢҒз»ӯдҝқжҢҒеңЁ11 g/dLд»ҘдёҠпјӣHbFжҜ”дҫӢд»Һеҹәзәҝзҡ„3.5%еҚҮиҮіз¬¬3дёӘжңҲзҡ„62.2%пјҢHbSжҜ”дҫӢд»Һеҹәзәҝзҡ„76.1%йҷҚиҮіз¬¬3дёӘжңҲзҡ„31.6%пјҢжІ»з–—еҗҺ3дёӘжңҲиө·пјҢHbFдёҺHbSжҜ”дҫӢжҢҒз»ӯзЁіе®ҡеңЁ6:4гҖӮжҲӘиҮіж•°жҚ®жҲӘжӯўж—ҘжңҹпјҲ2026е№ҙ5жңҲ24ж—ҘпјүпјҢжӮЈиҖ…е·ІйҡҸи®ҝ15.5дёӘжңҲпјҢйҡҸи®ҝжңҹеҶ…жңӘеҶҚеҮәзҺ°д»»дҪ•VOCгҖӮ

еӣҫ2 | SCDжӮЈиҖ…дёҙеәҠж•°жҚ®

A. жӮЈиҖ…1зҡ„жҖ»иЎҖзәўиӣӢзҷҪгҖҒHbFгҖҒHbAгҖҒHbSеҸҠHbA2зҡ„иЎЁиҫҫж°ҙе№ійҡҸж—¶й—ҙеҸҳеҢ–зҡ„и¶ӢеҠҝпјҢn= 1гҖӮеҹәзәҝзҷҫеҲҶжҜ”дәҺ研究е…Ҙз»„ж—¶пјҲ第0дёӘжңҲпјүжөӢе®ҡгҖӮ

B. жӮЈиҖ…1зҡ„Fз»ҶиғһеҚ жҜ”йҡҸж—¶й—ҙеҸҳеҢ–зҡ„и¶ӢеҠҝпјҢn= 1гҖӮFз»ҶиғһеҹәзәҝзҷҫеҲҶжҜ”дәҺ研究е…Ҙз»„ж—¶пјҲ第0дёӘжңҲпјүжөӢе®ҡгҖӮ

C. жӮЈиҖ…1еңЁеӣһиҫ“еҗҺеҸ‘з”ҹзҡ„VOCдәӢ件гҖӮ

D. жӮЈиҖ…1еңЁеӣһиҫ“еҗҺеҸ‘з”ҹзҡ„зәўз»Ҷиғһиҫ“жіЁдәӢ件гҖӮеӣһиҫ“еҗҺжүҖжңүзәўз»Ҷиғһиҫ“жіЁеқҮжҢү照研究方жЎҲжү§иЎҢгҖӮжҙ—и„ұжңҹжҢҮжң«ж¬Ўзәўз»Ҷиғһиҫ“жіЁеҗҺзҡ„60еӨ©жңҹй—ҙгҖӮ

еңЁдёүеҗҚTDTжӮЈиҖ…дёӯпјҢдёӯжҖ§зІ’з»ҶиғһжӨҚе…ҘдёӯдҪҚж—¶й—ҙдёә13еӨ©пјҲиҢғеӣҙпјҡ13-14еӨ©пјүпјҢиЎҖе°ҸжқҝжӨҚе…ҘдёӯдҪҚж—¶й—ҙдёә27еӨ©пјҲиҢғеӣҙпјҡ20-52еӨ©пјүпјӣжҖ»иЎҖзәўиӣӢзҷҪеҸҠHbFж°ҙе№іеҝ«йҖҹдё”жҳҫи‘—еҚҮй«ҳпјҢжІ»з–—еҗҺ第3дёӘжңҲпјҢе№іеқҮжҖ»иЎҖзәўиӣӢзҷҪиҫҫ11.6Вұ1.2 g/dLпјҢе№іеқҮHbFиҫҫ9.8 g/dLпјҲиҢғеӣҙпјҡ8.6-12 g/dLпјүпјӣдёӯдҪҚйҡҸи®ҝ17.5дёӘжңҲпјҲиҢғеӣҙпјҡ15.3-25.2дёӘжңҲпјүпјҢеқҮе®һзҺ°дәҶжҢҒз»ӯж‘Ҷи„ұиҫ“иЎҖдҫқиө–зҡ„зӣ®ж ҮгҖӮ

еӣҫ3 | TDTжӮЈиҖ…дёҙеәҠж•°жҚ®

A. жӮЈиҖ…2-4зҡ„жҖ»иЎҖзәўиӣӢзҷҪгҖҒHbFгҖҒHbAгҖҒHbEеҸҠHbA2зҡ„иЎЁиҫҫж°ҙе№ійҡҸж—¶й—ҙеҸҳеҢ–зҡ„и¶ӢеҠҝпјҢn= 1гҖӮеҹәзәҝзҷҫеҲҶжҜ”дәҺ研究е…Ҙз»„ж—¶пјҲ第0дёӘжңҲпјүжөӢе®ҡгҖӮ

B. жӮЈиҖ…2-4зҡ„Fз»ҶиғһеҚ жҜ”йҡҸж—¶й—ҙеҸҳеҢ–зҡ„и¶ӢеҠҝпјҢn= 1гҖӮFз»ҶиғһеҹәзәҝзҷҫеҲҶжҜ”дәҺ研究е…Ҙз»„ж—¶пјҲ第0дёӘжңҲпјүжөӢе®ҡгҖӮ

C. жӮЈиҖ…2-4еңЁеӣһиҫ“еҗҺеҸ‘з”ҹзҡ„зәўз»Ҷиғһиҫ“жіЁдәӢ件гҖӮ移жӨҚеҗҺжүҖжңүзәўз»Ҷиғһиҫ“жіЁеқҮжҢү照研究方жЎҲжү§иЎҢгҖӮжҙ—и„ұжңҹжҢҮжң«ж¬Ўзәўз»Ҷиғһиҫ“жіЁеҗҺзҡ„60еӨ©жңҹй—ҙгҖӮ

иҜҘ研究иҜҒе®һдәҶtBEе№іеҸ°еңЁдёҚеҗҢйҒ—дј иғҢжҷҜзҡ„ОІ-иЎҖзәўиӣӢзҷҪз—…жӮЈиҖ…дёӯе…·жңүиүҜеҘҪзҡ„е®үе…ЁжҖ§е’Ңжңүж•ҲжҖ§пјҢдёәе…ЁзҗғиҢғеӣҙеҶ…жӣҙе№ҝжіӣзҡ„жӮЈиҖ…зҫӨдҪ“жҸҗдҫӣдәҶжҪңеңЁзҡ„дёҖж¬ЎжҖ§жІ»ж„Ҳж–№жЎҲгҖӮ

дёҠжө·з§‘жҠҖеӨ§еӯҰз”ҹе‘Ҫ科еӯҰдёҺжҠҖжңҜеӯҰйҷўеҹәеӣ зј–иҫ‘дёӯеҝғйҷҲдҪіж•ҷжҺҲгҖҒеӨҚж—ҰеӨ§еӯҰз”ҹзү©еҢ»еӯҰ研究йҷў/еӨҚж—ҰеӨ§еӯҰйҷ„еұһе„ҝ科еҢ»йҷўжқЁеҠӣж•ҷжҺҲгҖҒжӯЈеәҸз”ҹзү©йҰ–еёӯжү§иЎҢе®ҳзүҹжҷ“зӣҫгҖҒеӨҚж—ҰеӨ§еӯҰйҷ„еұһе„ҝ科еҢ»йҷўзҝҹжҷ“ж–Үж•ҷжҺҲгҖҒе№ҝиҘҝеҢ»з§‘еӨ§еӯҰ第дёҖйҷ„еұһеҢ»йҷўиө–ж°ёжҰ•ж•ҷжҺҲдёәиҜҘи®әж–Үзҡ„е…ұеҗҢйҖҡи®ҜдҪңиҖ…гҖӮе№ҝиҘҝеҢ»з§‘еӨ§еӯҰ第дёҖйҷ„еұһеҢ»йҷўиЎҖж¶ІеҶ…科еҲҳе®№е®№ж•ҷжҺҲгҖҒиө–ж°ёжҰ•ж•ҷжҺҲпјҢдёҠжө·з§‘жҠҖеӨ§еӯҰи®ҝй—®еӯҰиҖ…зҺӢдёҪжҙҒпјҢеӨҚж—ҰеӨ§еӯҰйҷ„еұһе„ҝ科еҢ»йҷўй’ұжҷ“ж–Үж•ҷжҺҲпјҢеӨҚж—ҰеӨ§еӯҰз”ҹзү©еҢ»еӯҰ研究йҷўйқ’е№ҙ研究е‘ҳ马ж—ӯеҮҜдёәиҜҘи®әж–Үе…ұеҗҢ第дёҖдҪңиҖ…гҖӮ

еҺҹж–Үй“ҫжҺҘпјҡhttps://doi.org/10.1016/j.stem.2026.08.009