Oligonucleotides for inducing paternal UBE3A expression
The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.
1. An antisense oligonucleotide wherein the oligonucleotide is the oligonucleotide compound TTAcActtaattatactTCC (SEQ ID NO: 626) wherein capital letters represent beta-D-oxy LNA nucleosides, lowercase letters represent DNA nucleosides, all LNA C are 5-methyl cytosine, and all internucleoside linkages are phosphorothioate internucleoside linkages.
2. A pharmaceutical composition comprising the oligonucleotide of claim 1 and a pharmaceutically acceptable diluent, solvent, carrier, salt and/or adjuvant.
3. The pharmaceutical composition according to claim 2 wherein the pharmaceutically acceptable diluent includes phosphate-buffered saline (PBS).
4. The pharmaceutical composition according to claim 2 wherein the pharmaceutically acceptable salt is a sodium salt.
5. The pharmaceutical composition according to claim 2 wherein the pharmaceutically acceptable salt is a potassium salt.