Patent ID: 11872290
Assignee: ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL)
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC A  C

Claim 5:
6. A method of treating a motoneuron disease comprising:
administering to a subject in need thereof a bicistronic expression vector for silencing a gene specifically in astrocytes and neurons,
wherein the bicistronic expression vector comprises
a first expression cassette comprising a first silencer sequence and
a second expression cassette comprising a second silencer sequence,
wherein the expression of said first silencer sequence within astrocytes is regulated by an astrocyte-specific promoter and the expression of said second silencer sequence within neurons is regulated by a neuron-specific promoter;

wherein said bicistronic expression vector comprises two expression cassettes, wherein
the first expression cassette comprises “astrocyte specific promoter-posttranscriptional regulatory element-the first silencer sequence-polyA tail”, and
the second expression cassette comprises “neuron specific promoter-posttranscriptional regulatory element-the second silencer sequence-polyA tail” for silencing a gene in astrocytes and neurons,
wherein said first and second silencer sequences are both a miRNA designed to suppress SOD1 expression and
wherein
(i) said miR SOD1 targets the coding sequence of human SOD1 Genbank accession NM 000454.4, nt 209-229 (miR SOD1) (SEC) ID NO: 2); or,
(ii) said miRNA sequence comprises a 6 or 7 nucleotides-long “seed” sequence which is fully homologous to the human SOD1 mRNA transcript Genbank accession NM 000454.4; or,
(iii) said first and second silencer sequences are both a miRNA designed to suppress SOD1 expression and wherein said miR SOD1 mature sequence has at least 50%, at least 60%, at least 80%, or at least 90% seauence identity with the corresponding coding sequence set forth in SEQ ID NO: 1: 5′ATT ACT TTC CTT CTG CTC GAA-3′ (SEQ ID NO: 1).