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Optogenic Vision Restoration – Rare Diseases 2012

Redaktion

Für den Inhalt der Angaben zeichnet die Projektleitung verantwortlich.

Kooperation

This project is one of the six winners of the call 2012 «Rare Diseases - New Approaches». This is a collaborative effort by a number of groups around the world led by Jose Alain Sahel and Serge Picaud, at the Vision Institute of Paris, Jean Bennett at the University of Pennsylvania, Ernst Bamberg at the Max Planck Institute Frankfurt, Connie Cepko and Luk Vandenberghe at Harvard medical School and Botond Roska at the Friedrich Miescher Institute. The basic science, preclinical and clinical investigations by these groups will be put together into a product for patients by a company, GenSight Inc. Paris, led by Bernard Gilly.

Projektdaten

  • Projekt-Nr: GRS-039/12 
  • Förderbeitrag: CHF 500'000 
  • Bewilligung: 02.11.2012 
  • Dauer: 12.2012 - 08.2016 
  • Handlungsfeld:  Rare Diseases, 2009 - 2014

Projektleitung

Projektbeschreibung

Our goal is restore visual function in patients suffering in retinitis pigmentosa, using optogenetic technologies.

Retinitis pigmentosa (RP) collectively refers to a diverse group of progressive, hereditary rare diseases of the retina that lead to incurable blindness and affect two million people worldwide. Artificial photoreceptors constructed by expressing light-activated channels or pumps (‘optogenetic tools’) in surviving cell types in the retinal circuit have been shown to restore photosensitivity in animal models of RP. Our work here focuses on making efficient transfer of optogenetic tools to selected cell types in the retina and restoring color vision in animal models of RP. We believe that the results we obtain will bring optogenetic vision restoration closer to clinical use.

Was ist das Besondere an diesem Projekt?

The novel idea underlying optogenetic vision restoration is the use of light sensors from microbes to create artificial photoreceptors in the retina. The rational for using these sensors is that microbes use a single protein to detect and signal light while in mammals the interaction of more than ten proteins is needed for this purpose.

Stand/Resultate

We have made more than 200 new targeting vectors to selectively express optogenetic tools in different retinal cell types. We tested several of these vectors in vivo in the retinas in blind mice as well as in the retinas of wild type mice. We found about 20 different AAV vectors that target specific cell types or combination of cell types. We now have AAV vectors that can target cones, rods, Muller cells, some bipolar cell types, several amacrine cells types and several ganglion cell types in mice. A number of these AAVs are currently tested for targeted gene therapy applications. GenSight Biologics will translate cell type targeted gene therapy to human patients.

Publikationen

Yonehara K, Fiscella M, Drinnenberg A, Esposti F, Trenholm S, Krol J, Franke F, Scherf BG, Kusnyerik A, Müller J, Szabo A, Jüttner J, Cordoba F, Reddy AP, Németh J, Nagy ZZ, Munier F, Hierlemann A, Roska B. Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity. Neuron. 2016 Jan 6;89(1):177-93.
Krol J, Krol I, Alvarez CP, Fiscella M, Hierlemann A, Roska B* and Filipowicz W*. A network comprising short and long noncoding RNAs and RNA helicase controls mouse retina architecture. (*shared corresponding authors) Nature Communications 2015 Jun 4;6:7305.
Szikra T, Trenholm S, Drinnenberg A, Juettner J, Raics Z, Farrow K, Biel M, Awatramani G, Clark D, Sahel JA, da Silveira RA, Roska B During daylight rods act as relay cells conveying cone-driven horizontal cell-mediated surround inhibition to downstream visual circuits. Nature Neuroscience. 2014, 17(12):1728-35.
Busskamp V, Krol J, Nelidova D, Daum J, Szikra T, Tsuda B, Juettner J, Farrow K, Gross Scherf B, Patino Alvarez CP, Genoud C, Sothilingam V, Tanimoto N, Stadler M, Seeliger M, Stoffel M, Filipowicz W*, Roska B* MiRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function (*shared corresponding authors) Neuron. 2014, 83(3):586-600.
Cronin T, Vandenberghe LH, Hantz P, Juttner J, Reimann A, Kacsó AE, Huckfeldt RM, Busskamp V, Kohler H, Lagali PS, Roska B, Bennett J. Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter. EMBO Mol Med. 2014 Aug 4;6(9):1175-90.
Busskamp V, Duebel J, Balya D, Fradot M, Viney TJ, Siegert S, Groner AC, Cabuy E, Forster V, Seeliger M, Biel M, Humphries P, Paques M, Mohand-Said S, Trono D, Deisseroth K, Sahel JA, Picaud S, Roska B. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science. 2010 Jul 23;329(5990):413-7.
Lagali PS, Balya D, Awatramani GB, Münch TA, Kim DS, Busskamp V, Cepko CL, Roska B. Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nature Neurosci. 2008 Jun;11(6):667-75.
Siegert S, Cabuy E, Scherf BG, Kohler H, Panda S, Le YZ, Fehling HJ, Gaidatzis D, Stadler MB, Roska B. Transcriptional code and disease map for adult retinal cell types. Nature Neurosci. 2012 Jan
22;15(3):487-95.
Yonehara K, Farrow K, Ghanem A, Hillier D, Balint K, Teixeira M, Jüttner J, Noda M, Neve R, Conzelmann KK, Roska B. The first stage of cardinal direction selectivity is localized to the dendrites of retinal ganglion cells. Neuron. 2013, 79(6):1078-85.
Busskamp V, Krol J, Nelidova D, Daum J, Szikra T, Tsuda B, Juettner J, Farrow K, Gross Scherf B, Patino Alvarez CP, Genoud C, Sothilingam V, Tanimoto N, Stadler M, Seeliger M, Stoffel M, Filipowicz W*, Roska B* MiRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function (*shared corresponding authors) Neuron. 2014 Jul 4. [Epub ahead of print].

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Am Projekt beteiligte Personen

Letzte Aktualisierung dieser Projektdarstellung  09.10.2018