Abstract: A chimeric opsin GPCR protein comprising a light-sensitive upstream opsin portion and a target GPCR portion comprising a chimeric CT is provided that expresses strongly and is targeted into the correct subcellular compartment of target cells. The chimeric opsin GPCR protein activates efficiently the native G-protein specific to the target GPCR pathway eliciting a physiological response comparable to the native target GPCR. Nucleic acid molecules encoding the chimeric opsin GPCR protein as well as a capsids, vectors, cells and carriers comprising or expressing the chimeric opsin GPCR protein are also provided. Furthermore, a method of genetically engineering a chimeric opsin GPCR protein and medical applications of the chimeric opsin GPCR protein are provided.

Abstract: A light-sensitive chimeric protein includes domains from at least two members of the G-protein-coupled-receptor (GPCR) protein super family, which are fused to yield a light-sensitive GPCR chimera capable of coupling a light signal to the signaling cascade of the metabotropic glutamate receptor 6 (mGluR6) is provided for medical therapy and pharmaceuticals for treating loss of vision, in particular resulting from retinal photoreceptor degeneration. A first GPCR family member contributes domains which mediate the light-sensitivity to the chimeric light-sensitive GPCR protein and belongs to the family of light-sensitive GPCR proteins also called photopigments. In some cases, the GPCR protein is melanopsin, in particular human melanopsin. A second of the at least two GPCR family members is mGluR6, which contributes domains for coupling the light signal to the intracellular signaling cascade of mGluR6, which is a native component of the cell membrane of ON-bipolar cells in the inner retina.

Abstract: A light-sensitive chimeric protein comprising domains from at least two members of the G-protein-coupled-receptor (GPCR) protein super family, which are fused to yield a light-sensitive GPCR chimera capable of coupling a light signal to the signaling cascade of the metabotropic glutamate receptor 6 (mGluR6) is provided for medical therapy and for the manufacture of medicaments for improving vision, in particular for treating loss of vision resulting from retinal photoreceptor degeneration. A first of the at least two GPCR family members contributes domains which mediate the light-sensitivity to the chimeric light-sensitive GPCR protein. This first member belongs to the family of light-sensitive GPCR proteins also called photopigments, and in some embodiments this light-sensitive GPCR protein is melanopsin, in particular human melanopsin.