20-02-2014 дата публикации
Номер: US20140051748A1
Принадлежит:
The invention provides optimized miRNA sequences and their therapeutic use. The invention provides optimized miRNA constructs for treatment of neurodegenerative diseases. 1. An engineered mammalian pre-miR-XXX (pre-smiR-XXX) capable of forming a smiRNA/smiRNA* stem-loop structure comprising the following nucleic acid sequences in the 5′ to 3′ direction: [Gn]-[Nm]-[Ns]-[N*r]-UU , wherein [Nm] comprises [smiRNA-XXX] , [Ns] is a loop sequence of a corresponding endogenous pre-miR-XXX , [N*r] comprises [smiRNA*-XXX] , and wherein n=0-5 , s , m and r are determined by the sequences in the endogenous pre-miR-XXX , and wherein the smiRNA-XXX sequence is complementary to a target sequence of a miR-XXX derived from the corresponding endogenous pre-miR-XXX , wherein more than 7 bases of the smiRNA-XXX sequence are complementary to a seed sequence of the target sequence.2. An engineered mammalian pre-miR-XXX (pre-smiR-XXX) capable of forming a smiRNA/smiRNA* stem-loop structure comprising the following nucleic acid sequences in the 5′ to 3′ direction: [Gn]-[N*r]-[Ns]-[Nm]-UU , wherein [N*r] comprises [smiRNA*-XXX] , [Ns] is the loop sequence of a corresponding endogenous pre-miR-XXX , [Nm] comprises [smiRNA-XXX] , and wherein n=0-5 , s , m and r are determined by the sequences in the endogenous pre-miR-XXX , and wherein the smiR-XXX sequence is complementary to a target sequence of a miR-XXX derived from the corresponding endogenous pre-miR-XXX , wherein more than 7 bases of the smiRNA-XXX sequence are complementary to a seed sequence of the target sequence.3. An engineered mammalian pre-miR-XXX (pre-smiR-XXX) capable of forming a smiRNA-XXX-5p/smiRNA-XXX-3p stem-loop structure comprising the following nucleic acid sequences in the 5′ to 3′ direction: [Gn]-[Nm]-[Ns]-[Nr]-UU , wherein [Nm] comprises [smiR-XXX-5p] , [Ns] is the loop sequence of a corresponding endogenous pre-miR-XXX , [Nr] comprises [smiR-XXX-3p] , and wherein n=0-5 , s , m and r are determined by the sequences ...
Подробнее