Double-stranded RNA (dsRNA) and method of use for inhibiting expression of a fusion gene
View Patent ↗The present invention relates to the specific inhibition of expression of a fusion gene in mammals using a short double stranded RNA. The dsRNA is approximately 19-24 nucleotides in length, and has a nucleotide sequence which is complementary to at least a part of the target gene. The dsRNAs of the present invention are useful for treating diseases caused by chromosomal aberrations, particularly malignant diseases such as lymphoma and leukemia.
1. A method for inhibiting the expression of an AML-1/MTG-8 fusion gene in a mammalian cell in vitro, comprising the steps of:
a) introducing into a mammalian cell a dsRNA, said dsRNA comprising two separate non-linked RNA strands, a S1 strand and a complementary RNA strand, wherein said S1 strand consists of SEQ ID NO: 1 and said complementary strands consists of SEQ ID NO: 2, and
b) maintaining the cell produced in step (a) under conditions and for a time sufficient to obtain degradation of mRNA of said target fusion gene, thereby inhibiting expression of said target fusion gene in the cell.
2. The method of claim 1 , wherein each RNA strand is between 20 and 23 nucleotides in length.
3. The method of claim 1 , wherein each RNA strand is 21 nucleotides in length.
4. The method of claim 1 , wherein at least one of said RNA strands has a nucleotide overhang on the 3′-terminus.
5. The method of claim 1 , wherein the cell is a leukocyte.
6. The method of claim 1 , wherein the cell is a myelogenic cell.
7. The method of claim 1 , wherein the RNA is produced by chemical synthesis.
8. The method of claim 1 , wherein said S1 strand consists of SEQ ID NO: 1 and said complementary strand consists of SEQ ID NO: 2.