MODIFIED HUMAN U1myRNA MOLECULE, GENE CODING THE MODIFIED HUMAN U1myRNA MOLECULE, EXPRESSION VECTOR CONTAINING A GEN, AND THEIR APPLICATION IN GENE THERAPY
УНИВЕРСИТАДЕЛЬИ СТУДИ ДИ ФЕРРАРА (IT);УНИВЕРСИТА'ДЕЛЬИ СТУДИ ДИ ФЕРРАРА (IT)
发明人:
ПАГАНИ Франко (IT),ПИНОТТИ Мирко (IT)
申请号：
RU2013122109/10
公开号：
RU2013122109A
申请日:
2011.10.14
申请国别(地区):
RU
年份:
2014
代理人:
摘要：
1. A modified human U1myRNA molecule capable of correcting exon skipping caused by a mutation located in a sequence located between 50 base pairs above and 20 base pairs below the exon, the modified human U1myRNA molecule being characterized in that a portion of the single-stranded nucleotide sequence of the 5′-region wild-type human U1myRNA molecules are replaced by a single-stranded binding nucleotide sequence capable of hybridizing with the target nucleotide sequence pre-mRNA transcribed from a target gene of therapeutic interest carrying a mutation that causes an exon skip selected from the group consisting of mutations in a sequence located between 50 base pairs above and 20 base pairs below the exon, the target sequence being located in the region of the pre-mRNA of the target gene located between 2 and 50 base pairs below the portion of the splicing border, the splicing of which is affected by the indicated mutation. 2. The modified human U1myRNA molecule according to claim 1, where the portion of the 5′-region, which is replaced by a binding nucleotide sequence, is from 9 to 20 nucleotides in length. The modified human U1myRNA molecule according to claim 1 or 2, wherein the target gene of therapeutic interest is the coagulation factor IX gene, the SMN2 gene, or the CFTR.4 gene. The modified human U1myRNA molecule according to claim 1, wherein the binding nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.5. The modified human U1myRNA molecule according to claim 1 for use in the therapeutic treatment of genetic1. Модифицированная молекула U1мяРНК человека, способная исправлять пропуск экзона, вызванный мутацией, которая расположена в последовательности, находящейся между 50 парами оснований выше и 20 парами оснований ниже экзона, причем модифицированная молекула U1мяРНК человека отличается тем, что участок одноцепочечной нуклеотидной последовательности 5′-области молекулы U1мяРНК человека дикого типа замещен
