鏍哥硸鏍擱吀鍦ㄥ尰瀛﹂鍩熺殑搴旂敤涓昏闆嗕腑鍦ㄥ熀鍥犳矇榛樸�佸熀鍥犱慨澶嶅拰璋冩帶鍩哄洜琛ㄨ揪絳夋柟闈紝榪欎簺鎶�鏈凡琚瘉鏄庡湪娌葷枟鐧岀棁銆侀仐浼犵柧鐥呭拰鐥呮瘨鎰熸煋絳夋柟闈㈠叿鏈夋樉钁楁晥鏋溿�傚叾楂樺害鐗瑰紓鎬у拰浣庢瘨鎬т嬌鍏惰兘澶熺簿紜澏鍚戠壒瀹氬熀鍥狅紝鍑忓皯鍓綔鐢ㄣ�傝繖縐嶉珮搴︾壒寮傛�у拰浣庢瘨鎬х殑鐗硅川錛屼篃浣垮緱鏍哥硸鏍擱吀鍦ㄦ姉琛拌�併�佺毊鑲や慨澶嶅拰娌葷枟鐐庣棁鎬х毊鑲ょ梾鏂歸潰灞曠幇鍑哄法澶ф綔鍔涳紝鎴愪負(fù)鐜頒唬鎶よ偆縐戞妧鐨勬柊鍏村埄鍣ㄣ�?/span>
緹庢⒌寰″湪鍗楁柟鍖葷瀛ｇ埍姘戞暀鎺堝甫棰嗙殑涓撲笟縐戠爺鍥㈤槦錛屾垚鍔熷皢鏍哥硸鏍擱吀鎶�鏈簲鐢ㄥ埌鎶よ偆棰嗗煙涓�?/span>
鏍哥硸鏍擱吀鐨勫熀鏈蹇靛拰綾誨瀷
鏍哥硸鏍擱吀錛?/span>Small Nucleic Acids錛夛細(xì)鏍哥硸鏍擱吀鏄竴綾葷煭閾炬牳閰稿垎瀛愶紝閫氬父闀垮害鍦?/span>20-30涓牳鑻烽吀宸﹀彸錛岃兘澶熺壒寮傛�у湴緇撳悎鐩爣RNA鎴?/span>DNA鍒嗗瓙錛屼粠鑰岃皟鎺у熀鍥犺〃杈俱�傝繖浜?/span>鏍哥硸鏍擱吀鍖呮嫭浠ヤ笅鍑犵涓昏綾誨瀷錛?/span>
1. 灝忓共鎵?/span>RNA錛?/span>siRNA錛夛細(xì)
瀹氫箟錛氱敱鍙岄摼RNA鍒嗗瓙杞寲鑰屾潵鐨勭煭閾?/span>RNA錛岄�氳繃寮曞RNA璇卞娌夐粯澶嶅悎鐗╋紙RISC錛夎瘑鍒拰鍒囧壊鐗瑰畾鐨?/span>mRNA錛屼粠鑰屾姂鍒跺熀鍥犺〃杈俱�傚姛鑳斤細(xì)涓昏鐢ㄤ簬鍩哄洜娌夐粯鍜岃皟鎺э紝鏄?/span>RNA騫叉壈錛?/span>RNAi錛夋妧鏈殑鍩虹銆?/span>
2. 寰?/span>RNA錛?/span>miRNA錛夛細(xì)
瀹氫箟錛氬唴婧愭�х殑鍗曢摼RNA鍒嗗瓙錛岄�氳繃涓庣洰鏍?/span>mRNA鐨?/span>3'闈炵炕璇戝尯錛?/span>UTR錛夐儴鍒嗙粨鍚堬紝鎶戝埗mRNA鐨勭炕璇戞垨淇冭繘鍏墮檷瑙ｃ�?/span>
鍔熻兘錛氬湪澶氱鐢熺墿榪囩▼涓彂鎸ラ噸瑕佽皟鎺т綔鐢紝鍖呮嫭鍙戣偛銆佸垎鍖栥�佸孌栧拰鍑嬩骸銆?/span>
3. 鍙嶄箟瀵℃牳鑻烽吀錛?/span>ASO錛夛細(xì)
瀹氫箟錛氬崟閾?/span>DNA鎴?/span>RNA鍒嗗瓙錛屽彲浠ヤ笌鐩爣mRNA緇撳悎錛岄�氳繃闃繪柇mRNA鐨勭炕璇戞垨鏀瑰彉鍏跺壀鎺ユā寮忔潵璋冩帶鍩哄洜琛ㄨ揪銆?/span>
鍔熻兘錛氱敤浜庢不鐤楀縐嶉仐浼犵柧鐥呭拰鍏朵粬鐥呯悊鐘舵�併�?/span>
4. 鏍擱叾錛?/span>Ribozyme錛夛細(xì)
瀹氫箟錛氬叿鏈夊偓鍖栨椿鎬х殑RNA鍒嗗瓙錛屽彲浠ュ垏鍓茬壒瀹氱殑RNA閾撅紝浠庤�岃皟鎺у熀鍥犺〃杈俱�?/span>
鍔熻兘錛氫富瑕佸湪鐮旂┒鍜屾不鐤椾腑鐢ㄤ綔鍒嗗瓙鍓垁錛屽垏鍓茬壒瀹氱殑RNA鍒嗗瓙銆?/span>
鏍哥硸鏍擱吀鍦ㄧ毊鑲ょ敓鐞嗕腑鐨勪綔鐢ㄦ満鍒?/span>
鏍哥硸鏍擱吀鍦ㄧ毊鑲ょ敓鐞嗕腑鐨勪綔鐢ㄦ満鍒朵富瑕佸寘鎷互涓嬪嚑涓柟闈細(xì)
1.鏍哥硸鏍擱吀鎶戝埗榛戣壊绱?/span>
(1) 浣滅敤鏈哄埗錛?/span>鏍哥硸鏍擱吀鍙互闈跺悜榛戣壊绱犵敓鎴愮浉鍏沖熀鍥犵殑mRNA錛屾姂鍒跺叾琛ㄨ揪錛屼粠鑰屽噺灝戦粦鑹茬礌鐨勫悎鎴愩�傞�氳繃鐗瑰紓鎬х粨鍚堜笌榛戣壊绱犵敓鎴愮浉鍏崇殑鍏抽敭鍩哄洜錛堝閰皚閰擱叾銆?/span>TYRP1鍜?/span>TYRP2錛夌殑mRNA錛?/span>鏍哥硸鏍擱吀鍙互闃繪榪欎簺鍩哄洜鐨勭炕璇戯紝闄嶄綆榛戣壊绱犵敓鎴愰叾鐨勪駭閲忋�?/span>
(2) 搴旂敤紺轟緥錛氬湪緹庣櫧綺懼崕娑插拰娣℃枒闇滀腑錛岄�氳繃鎶戝埗榛戣壊绱犵敓鎴愬熀鍥犵殑琛ㄨ揪錛屽噺灝戠毊鑲よ壊绱犳矇鐫�錛屾敼鍠勮偆鑹蹭笉鍧囧拰鑹叉枒闂銆備緥濡傦紝浣跨敤siRNA鎶�鏈壒寮傛�ф姂鍒墮叒姘ㄩ吀閰跺熀鍥犵殑琛ㄨ揪錛岄厤鍚堝叾浠栫編鐧芥垚鍒嗭紝濡傜淮鐢熺礌C鍜岀儫閰拌兒錛屾樉钁楁彁楂樼編鐧芥晥鏋滐紝閫傜敤浜庨渶瑕佹貳鍖栬壊鏂戝拰鍧囧寑鑲よ壊鐨勬秷璐硅�呫�?/span>
2. 璋冩帶鍩哄洜琛ㄨ揪鍜岃泲鐧借川鍚堟垚錛?/span>
(1) 浣滅敤鏈哄埗錛?/span>鏍哥硸鏍擱吀鍙互閫氳繃鐗瑰紓鎬х粨鍚堢毊鑲ょ粏鑳?yōu)涓?/span>mRNA鍒嗗瓙錛屾姂鍒舵垨淇冭繘鐗瑰畾鍩哄洜鐨勮〃杈撅紝浠庤�岃皟鎺т笌鐨偆鍋ュ悍鍜屽姛鑳界浉鍏崇殑铔嬬櫧璐ㄧ殑鍚堟垚銆?/span>
(2) 搴旂敤紺轟緥錛氶�氳繃璋冩帶涓庤兌鍘熻泲鐧界敓鎴愮浉鍏崇殑鍩哄洜琛ㄨ揪錛屼績榪涚毊鑲ゅ脊鎬у拰绱ц嚧搴︾殑鎻愰珮銆?/span>
3.鎶戝埗鐐庣棁鍙嶅簲錛?/span>
(1) 浣滅敤鏈哄埗錛?/span>鏍哥硸鏍擱吀鍙互闈跺悜鐐庣棁鍥犲瓙鐨?/span>mRNA錛屾姂鍒跺叾琛ㄨ揪錛屼粠鑰屽噺灝戠値鐥囧弽搴斻�?/span>
(2) 搴旂敤紺轟緥錛氬湪娌葷枟鐥ょ柈銆佹箍鐤圭瓑鐨偆鐐庣棁鎬х柧鐥呬腑錛岄�氳繃鎶戝埗鐐庣棁浠嬭川鐨勭敓鎴愶紝鍑忚交鐨偆鐨勭値鐥囧弽搴斻�?/span>
4. 淇冭繘緇嗚優(yōu)淇涓庡啀鐢燂細(xì)
(1) 浣滅敤鏈哄埗錛?/span>鏍哥硸鏍擱吀鍙互璋冩帶涓庣粏鑳?yōu)澧瀸D栥�佸垎鍖栧拰鍑嬩骸鐩稿叧鐨勫熀鍥狅紝淇冭繘鐨偆緇嗚優(yōu)鐨勪慨澶嶄笌鍐嶇敓銆?/span>
(2) 搴旂敤紺轟緥錛氬湪鐨偆鍒涗激淇鍜屾姉琛拌�佹姢鑲ゅ搧涓紝閫氳繃淇冭繘鏂扮粏鑳?yōu)鐨勭敓鎴愬拰鏃Ьl嗚優(yōu)鐨勪慨澶嶏紝鏀瑰杽鐨偆鐨勫仴搴風(fēng)姸鎬佸拰澶栬銆?/span>
榪欎簺浣滅敤鏈哄埗浣垮緱鏍哥硸鏍擱吀鍦ㄦ姢鑲ら鍩熷叿鏈夊箍娉涚殑搴旂敤娼滃姏錛岃兘澶熼拡瀵瑰縐嶇毊鑲ら棶棰樻彁渚涙柊鐨勬不鐤楀拰鎶ょ悊鏂規(guī)硶銆?/span>