JIN, Xiaomei,YU, Lei,TAKAHASHI, Hirokazu,TANAKA, Yasunobu,NIITSU, Yoshiro,FEINSTEIN, Elena,AVKIN-NACHUM, Sharon,KALINSKI, Hagar,METT, Igor,ERLICH, Shai,SQUIERS, Elizabeth C.,CHEN, Ning
申请号:
ES10836656
公开号:
ES2562499T3
申请日:
2010.12.08
申请国别(地区):
ES
年份:
2016
代理人:
摘要:
A double-stranded nucleic acid molecule having the structure (A2) set forth below: (A2) 5 'N1- (N) x- Z 3' (antisense strand) 3 'Z'-N2- (N') and z "5 '(coding strand) in which each of N2, N and N' is an unmodified or modified ribonucleotide or an unconventional moiety; in which each of (N) xy (N ') and is an oligonucleotide in which each consecutive N or N 'is linked to the adjacent N or N' by a covalent bond; in which each of x and y is independently an integer between 17 and 39; in which the sequence of (N ') and has complementarity with the sequence of (N) xy (N) x has complementarity with a consecutive sequence in an mRNA of hsp47 (SEQ ID NO: 1); in which N1 is covalently linked to (N) xy is missing with the mRNA of hsp47 or is a DNA moiety complementary to hsp47 mRNA; in which N1 is a moiety selected from the group consisting of uridine, deoxyribouridine, ribothymidine, deoxyribothymidine, adenosine or desooxyadenosine natura les or modified; where z '' may be present or absent, but if present it is a cap rest covalently connected to the 5 'end of N2- (N') and; wherein each of Z and Z 'is independently present or absent, but if present it is independently 1-5 consecutive nucleotides, consecutive non-nucleotide moieties or a combination thereof covalently connected to the 3' end of the strand in which is present; and wherein the antisense strand comprises an antisense sequence of SEQ ID NO: 127.Una molécula de ácido nucleico bicatenaria que tiene la estructura (A2) expuesta a continuación: (A2) 5' N1-(N)x- Z 3' (hebra anticodificante) 3' Z'-N2-(N')y-z" 5' (hebra codificante) en la que cada uno de N2, N y N' es un ribonucleótido no modificado o modificado o un resto no convencional; en la que cada uno de (N)x y (N')y es un oligonucleótido en que cada N o N' consecutivo está unido al N o N' adyacente por un enlace covalente; en la que cada uno de x e y es independientemente un entero entre 17 y 39; en la que la secuencia de (N')y tiene complementariedad con la sec