Institut National De La Sante Et De La Recherche Medicale

Centre National De La Recherche Scientifique

Sorbonne Université

Université Pierre Et Marie Curie (Paris 6)

Friedrich Miescher Institute for Biomedical Research

Technische Universitát Dresden

Inserm

Deniz Dalkara

Jose-Alain Sahel

Jens Duebel

Botond Roska

Thierry Leveillard

Serge Picaud

Olivier Goureau

Alvaro Rendon Fuentes

Ophelie Vacca

Alexis Bemelmans

Hanen Khabou

Melissa Desrosiers

José-Alain Sahel

Marius Ader

Antoine Chaffiol

Marcela Garita-hernandez

Marusa Lampic

Several new vector-promoter combinations to overcome the limitations associated with AAV-mediated cone transduction in the fovea are provided. The delivery modality relies on a cone-specific promoter and result in high-level transgene expression compatible with optogenetic vision restoration. Methods of expressing a polynucleotide of interest in the cone photoreceptors of a subject comprising subretinal delivery of a therapeutically effective amount of a recombinant AAV9-derived vector comprising a VP1 capsid protein as set forth in SEQ ID NO: 11 and the polynucleotide of interest under the control of the pR1.7 promoter as set forth in SEQ ID NO: 12 are also provided.

Methods of expressing a polynucleotide of interest in the cone photoreceptors of a subject comprising the subretinal delivery of a therapeutically effective amount of a recombinant AAV9-derived vector

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

Provided herein are methods for expressing a polynucleotide of interest in the retina of a subject. In particular, a method for expressing a polynucleotide of interest in the retina of a subject comprising the step consisting of injecting into the vitreous an amount of a vector containing the polynucleotide of interest in combination with an amount of an inhibitor of Dp71 expression is provided.

Methods for expressing a polynucleotide of interest in the retina of a subject

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Alfortville, France

Deniz Dalkara