Micro RNA (MiRNA) and neurofibromatosis type 1: a role in diagnosis and therapy
View Patent ↗The present invention shows that levels of certain micro RNAs (MiRNAs) are altered in NF1 cell lines and NF1 tumor cell lines as compared to non-NF1 controls. Methods are provided, e.g., to diagnose NF1 and NF1 tumors. Methods are also provided to treat NF1, NF1 related cancer, and cognitive deficits resulting from NF1.
1. A method of increasing neurofibromin expression in a neural cell of a subject having neurofibromatosis type 1 comprising contacting the cell with an effective amount of a miR-10b inhibitor which downmodulates the level of miR-10 miRNA in the neural cell, such that neurofibromin expression in the neural cell is increased.
2. The method of claim 1 , wherein the miR-10b inhibitor is an miR-10b antigomir comprising a nucleotide sequence having complementarity to miR-10b.
3. The method of claim 2 , wherein the miR-10b antigomir comprises the nucleotide sequence 5′-CACAAATTCGGTTCTACAGGGTA-3′ [SEQ. ID NO.1].
4. The method of claim 2 , wherein the antigomir comprises at least one stabilizing modification.
5. The method of claim 4 , wherein the at least one stabilizing modification comprises a phosphorothioate backbone.
6. The method of claim 4 , wherein the at least one stabilizing modification comprises at least one nucleotide having a 2′-sugar modification.
7. The method of claim 1 , wherein the miR-10b inhibitor inhibits miR-10b indirectly by inhibiting TWIST1.
8. The method of claim 2 , wherein the antigomir is 19 to 24 nucleotides in length.
9. The method of claim 2 , wherein the antigomir has at least 95% percent complementarity to the miRNA over its full length, and wherein the 8 nucleotides at the 5′ end of the antigomir are 100% complementary to the corresponding nucleotides of the miRNA.
10. The method of claim 2 , wherein the antigomir comprises a cholesterol modification.