Friedrich Miescher Institute for Biomedical Research

Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Sorbonne Université

Inserm

Botond Roska

Josephine Juettner

Dominik Hartl

Arnaud Krebs

Dirk Schuebeler

Pamela Lagali

Volker Busskamp

Jacek Krol

Dasha Nelidova

David Balya

Jose-Alain Sahel

Serge Picaud

Deniz Dalkara

Jens Duebel

Alexis Bemelmans

Melissa Desrosiers

José-Alain Sahel

The present inventions relates to an isolated nucleic acid molecule comprising a nucleotide sequence coding for a depolarizing light-gated ion channel functionally linked to a promoter leading to the specific expression of said depolarizing light-gated ion channel in a retinal photoreceptor, or the nucleotide sequence complementary to said nucleotide sequence, for use in treating or ameliorating blindness. The present invention also relates to methods of using such nucleic acid molecules in the treatment of blindness.

Therapeutical tools and methods for treating blindness by targeting photoreceptors

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 300 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in rod photoreceptors of a gene when operatively linked to a nucleic acid sequence coding for said gene.

Expression cassette with a SynP160 promoter

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 150 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in rod photoreceptors of a gene when operatively linked to a nucleic acid sequence coding for said gene.

SYNP161, a promoter for the expression of genes

The present invention to a method for expressing an exogenous gene specifically in cells of the retinal pigment epithelium of a primate, this method comprising the step of delivering an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1, or consisting of a nucleic acid sequence of at least 400 bp having at least 80% overall identity to the sequence of SEQ ID NO:1, to cells of the retinal pigment epithelium of the primate, wherein this isolated nucleic acid molecule specifically leads to the expression of an exogenous gene in cells of the retinal pigment epithelium of primates when a nucleic acid sequence coding for the exogenous gene is operatively linked to this isolated nucleic acid molecule.

Primate retinal pigment epithelium cell-specific promoter

SYNP162, a promoter for the expression of genes

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 400 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in rod photoreceptors of a gene when operatively linked to a nucleic acid sequence coding for said gene.

SynP159, a promoter for the expression of genes

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 1000 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in cells of the retinal pigment epithelium of a gene when operatively linked to a nucleic acid sequence coding for said gene.

SynPIII, a promoter for the specific expression of genes in retinal pigment epithelium

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 400 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in direction selective retinal ganglion cells of a gene when operatively linked to a nucleic acid sequence coding for said gene.

SynP198, a promoter for the specific expression of genes in direction selective retinal ganglion cells

The present invention relates to a nucleic acid sequence derived from the regulatory region of the human gamma-synuclein gene and having a promoter activity in retinal ganglion cells. The present invention also relates to expression cassettes or vectors comprising said promoter operably linked to a nucleic acid sequence encoding a polypeptide of interest as well as viral particles or host cells comprising said expression cassette or vector. The present invention also relates to the use of said expression cassettes, vectors, viral particles or cells in the treatment of ocular disease, in particular ocular disease associated with retinal ganglion cell or photoreceptor cell degeneration.

Promoters and uses thereof

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 1800 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in retinal ganglion cells of a gene when operatively linked to a nucleic acid sequence coding for said gene.

SYNP88, a promoter for the specific expression of genes in retinal ganglion cells

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 600 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in retinal endothelial cells of a gene when operatively linked to a nucleic acid sequence coding for said gene.

Promoter for the specific expression of genes in retinal endothelial cells

SYNP162, a promoter for the specific expression of genes in rod photoreceptors

SYNP159, a promoter for the specific expression of genes in rod photoreceptors

SynP160, a promoter for the specific expression of genes in rod photoreceptors

The present invention relates to the use of an isolated nucleic acid molecule comprising a nucleotide sequence coding for a hyperpolarizing light-gated ion channel or pump gene from an archeon or for a light-active fragment of said gene, or the nucleotide sequence complementary to said nucleotide sequence, for treating or ameliorating blindness. The light-gated ion channel or pump gene can be a halorhodopsin gene.

Growing community of inventors

Oberwil, Switzerland

Botond Roska