申请人:ethris GmbH
公开号:EP3112469A1
公开(公告)日:2017-01-04
Described is an RNA molecule comprising (a) a coding region coding for a polypeptide; and (b) upstream of said coding region one or more UTR(s) comprising the sequence as shown in SEQ ID NO:1 or a sequence which shows 1 to 4 substitutions in comparison to SEQ ID NO:1 and which results in an RNA molecule having the same or a higher translation efficiency as an RNA molecule comprising an UTR comprising SEQ ID NO:1; and/or (c) downstream of said coding region one or more UTR(s) comprising the sequence as shown in SEQ ID NO:2 or a sequence which shows 1 to 7 substitutions in comparison to SEQ ID NO:2 and which results in an RNA molecule having the same or a higher translation efficiency as an RNA molecule comprising an UTR comprising SEQ ID NO:2; wherein said polypeptide encoded by said coding region is not a cytochrome b-245 alpha polypeptide (CYBA). Moreover, described is a nucleic acid molecule encoding the RNA molecule according to the present invention. Further, described is a vector comprising the nucleic acid molecule according to the present invention and to a host cell comprising the vector according to the present invention. Further, described is a pharmaceutical composition comprising the RNA molecule according to the present invention and optionally a pharmaceutically acceptable carrier. Moreover, described is a kit comprising the RNA molecule according to the present invention. Finally, described is the use of one or more UTR(s) as defined in (b) and/or one or more UTR(s) as defined in (c) for increasing the efficiency of translating a coding region of an RNA molecule into a polypeptide or a protein encoded by said coding region.
所述 RNA 分子包括(a)编码多肽的编码区;和(b)所述编码区上游的一个或多个 UTR,该 UTR 包括 SEQ ID NO:1 所示序列或与 SEQ ID NO:1 相比显示 1 至 4 个取代的序列,其产生的 RNA 分子与包括 SEQ ID NO.1 所示 UTR 的 RNA 分子具有相同或更高的翻译效率;和/或(c)所述编码区下游的一个或多个 UTR,该 UTR 包括 SEQ ID NO:2 所示序列或与 SEQ ID NO:1 相比显示 1 至 7 个取代的序列:1;和/或(c) 在所述编码区下游的一个或多个 UTR,其包含 SEQ ID NO:2 中所示的序列或与 SEQ ID NO:2 相比显示 1 至 7 个取代的序列,其导致的 RNA 分子与包含 SEQ ID NO:2 的 UTR 的 RNA 分子具有相同或更高的翻译效率;其中所述编码区编码的所述多肽不是细胞色素 b-245 alpha 多肽(CYBA)。此外,所述的是编码根据本发明的 RNA 分子的核酸分子。此外,还描述了一种包含根据本发明的核酸分子的载体和包含根据本发明的载体的宿主细胞。此外,还描述了一种药物组合物,该组合物包含根据本发明的 RNA 分子和可选的药学上可接受的载体。此外,还描述了一种包含根据本发明的 RNA 分子的试剂盒。最后,描述了(b)中定义的一个或多个 UTR 和/或(c)中定义的一个或多个 UTR 的用途,以提高将 RNA 分子的编码区翻译成由所述编码区编码的多肽或蛋白质的效率。