公开(公告)号：US20090306188A1

公开(公告)日：2009-12-10

申请号：US11913618

申请日：2006-05-03

申请人： Marisol Corral-Debrinski ,  José-Alain Sahel ,  Valérie Kaltimbacher ,  Crystel Bonnet

发明人： Marisol Corral-Debrinski ,  José-Alain Sahel ,  Valérie Kaltimbacher ,  Crystel Bonnet

IPC分类号： A61K31/7052 ,  C12N15/63 ,  C07H21/00 ,  C12N5/00 ,  A61P43/00

CPC分类号： C12N15/85 ,  A61K48/005 ,  A61K48/0058 ,  A61K48/0066 ,  C07K14/47 ,  C07K2319/07 ,  C12N9/0053 ,  C12N9/0089 ,  C12N9/1085 ,  C12N15/8509 ,  C12N2800/22 ,  C12N2810/80 ,  C12Y109/03001

摘要： The inventors demonstrate that mRNA sorting to the mitochondrial surface is an efficient way to proceed to such an allotopic expression, and that this mRNA sorting can be controlled by selecting appropriate mitochondrion-targeting sequence (MTS) and appropriate 3′UTR sequences. The CDS sequence which codes for the protein to be delivered into the mitochondrion is guided by these appropriate MTS and 3′UTR sequences from the nuclear compartment to the mitochondrion-bound polysomes (where the CDS is translated), and aids in an efficient translocation of a mature functional protein into the mitochondria. Appropriate MTS and 3′UTR sequences correspond to those of nuclearly-transcribed mitochondrially-targeted mRNAs. The inventors demonstrate that, to obtain a stable therapeutically-effective importation, both an appropriate MTS and an appropriate 3′UTR should preferably be used.

摘要翻译： 本发明人证明，对线粒体表面的mRNA分选是进行这种同种异体表达的有效方式，并且可以通过选择适当的线粒体靶向序列（MTS）和合适的3'UTR序列来控制该mRNA分选。 编码要递送到线粒体中的蛋白质的CDS序列由这些适当的MTS和3'UTR序列从核隔室引导到线粒体结合的多核糖体（其中CDS被翻译），并且有助于有效移位 成熟的功能蛋白进入线粒体。 适当的MTS和3'UTR序列对应于核转录的线粒体靶向mRNA的那些。 发明人证明，为了获得稳定的治疗有效的进口，优选使用适当的MTS和适当的3'UTR。