Tau antisense oligomers and uses thereof
The present invention relates to oligomer compounds (oligomers), which target Tau mRNA in a cell, leading to reduced expression of Tau protein. Reduction of Tau protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.
1. An oligomer consisting of the nucleic acid sequence AtTTCcaaattcactTTtAC (SEQ ID NO: 473), wherein upper case letters denote beta-D-oxy-LNA, and lower case letters denote DNA monomers.
2. The oligomer of claim 1 , which comprises an internucleoside linkage selected from: a phosphodiester linkage, a phosphotriester linkage, a methylphosphonate linkage, a phosphoramidate linkage, a phosphorothioate linkage, and combinations thereof.
3. The oligomer of claim 1 , wherein calcium oscillations of neuronal cells which are in contact with the oligomer are greater than or equal to 95%, greater than or equal to 90%, greater than or equal to 85%, greater than or equal to 80%, greater than or equal to 75%, or greater than or equal to 70% of oscillations in a cell not in contact with the oligomer.
4. The oligomer of claim 1 , which has at least one property selected from: (1) reduces expression of Tau mRNA in a cell, compared to a control cell that has not been exposed to the oligomer; and (2) reduces expression of Tau protein in a cell, compared to a control cell that has not been exposed to the oligomer.
5. A conjugate comprising the oligomer of claim 1 , wherein the oligomer is covalently attached to at least one non-nucleotide or non-polynucleotide moiety.
6. A composition comprising the oligomer of claim 1 and a pharmaceutically acceptable carrier.
7. A kit comprising the oligomer of claim 1 and instructions for use.
8. The oligomer of claim 1 , wherein all internucleoside linkages are phosphorothioate linkages.