Abstract: MECP2 EXPRESSION CASSETTES. The present invention provides nucleic acid molecules comprising a MeCP2 expression cassette, the expression cassette comprising, in operable linkage from 5? to 3?: a 5? transcriptional control region comprising a promoter capable of driving transcription in neural cells; an open reading frame encoding a MeCP2 protein; translation control signals; a 3? untranslated region (3?UTR) comprising one or more of: (i) a binding site for mir-22; (ii) a binding site for mir-19; (iii) a binding site for miR-132; (iv) a binding site for miR124; and (v) an AU-rich element; and transcriptional termination signals; wherein the MeCP2 expression cassette is not more than about 5 kb in length. The invention further provides viral vectors, especially vectors derived from adeno-associated virus (AAV), for use in therapeutic delivery of such expression cassettes.

Abstract: The present invention provides nucleic acid molecules comprising a MeCP2 expression cassette, the expression cassette comprising, in operable linkage from 5? to 3?: a 5? transcriptional control region comprising a promoter capable of driving transcription in neural cells; an open reading frame encoding a MeCP2 protein; translation control signals; a 3? untranslated region (3?UTR) comprising one or more of: (i) a binding site for mir-22; (ii) a binding site for mir-19; (iii) a binding site for miR-132; (iv) a binding site for miR124; and (v) an AU-rich element; and transcriptional termination signals; wherein the MeCP2 expression cassette is not more than about 5 kb in length. The invention further provides viral vectors, especially vectors derived from adeno-associated virus (AAV), for use in therapeutic delivery of such expression cassettes.

Abstract: MeCP2 based therapy. The present invention relates to synthetic polypeptides that are useful in the treatment of disorders associated with reduced MeCP2 activity, including Rett syndrome. The present invention provides synthetic polypeptides comprising: i) an MBD amino acid sequence showing at least 70% similarity with the amino acid sequence showing at least 70% similarity with the amino acid sequence as depicted in SEQ ID NO: 2, wherein the polypeptide has a deletion of at least 50 amino acids, when compared to the full length MeCP2 e1 and e2 sequences. The invention further provides nucleic acid constructs, expression vectors, virions, pharmaceutical compositions, and cells providing polynucleotides of the invention. The invention further provides methods of treating or preventing disease in an animal comprising administering to said animal a synthetic polypeptide according to the invention.

Abstract: The present invention provides nucleic acid molecules comprising a MeCP2 expression cassette, the expression cassette comprising, in operable linkage from 5? to 3?: a 5? transcriptional control region comprising a promoter capable of driving transcription in neural cells; an open reading frame encoding a MeCP2 protein; translation control signals; a 3? untranslated region (3?UTR) comprising one or more of: (i) a binding site for mir-22; (ii) a binding site for mir-19; (iii) a binding site for miR-132; (iv) a binding site for miR124; and (v) an AU-rich element; and transcriptional termination signals; wherein the MeCP2 expression cassette is not more than about 5 kb in length. The invention further provides viral vectors, especially vectors derived from adeno-associated virus (AAV), for use in therapeutic delivery of such expression cassettes.