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FLInChR

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FLInChR

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FLInChR : (Full Length Inverted Channelrhodopsin)

FLInChR is an engineered variant of a light-gated opsin, Channelrhodopsin, that functions as a potent optical inhibitor of neuronal activity.  Fusion to the ‘leader’ sequence results in the topological inversion of the opsin and converts it to a light-gated, non-specific cation pump. This ‘flipped’ opsin is efficient as an inhibitor of neuronal activity in both in vitro and in vivo. The ‘topological engineering’ of opsins used to generate FLInChR could serve as a robust platform to screen for variants of membrane-bound proteins with useful properties. Researchers could further use it to expand the optogenetic toolkit.

FLInChR can be expressed in vitro and in vivo in model organisms using DNA constructs (C. elegans) or AAV viral vectors (for rodents). For example, AAV-CAG-FLInChR-mVenus plasmid, distributed by Addgene, can be used to produce viral particles to transduce cells or organisms and express FLInChR in cell types of interest.

Photo stimulation of FLInChR, in vitro and in vivo, is achieved by lasers as described in the publication below (STAR Methods). Further details on the experimental setup are provided in the STAR Methods in the publication.

Advantages:
A general method to control the orientation of membrane-bound proteins, generating functional diversity. 
Optogenetic inactivator with potency and speed equivalent to the state-of-the-art Opsins. 
Spectrally shifted with respect to Channelrhosopsin.
 
Application:
Optogenetic inactivation of neurons (or any mammalian cell) expressing the channels both in vitro and in vivo. 
 
 
Publication:
Expanding the Optogenetics Toolkit by Topological Inversion of Rhodopsins. Brown J, Behnam R, Coddington L, Tervo DGR, Martin K, Proskurin M, Kuleshova E, Park J, Phillips J, Bergs ACF, Gottschalk A, Dudman JT, Karpova AY. Cell. 2018 Oct 16. pii: S0092-8674(18)31238-8.
 
Patent Status:
Pending PCT patent application PCT/US2019/035344
 
Opportunity:
Plasmid DNA encoding FLInChR-mVenus - AAV-CAG-FLInChR-mVenus - is available from Addgene for non-profit researchers - see the link to the right.
Commercial licenses are available. Please contact innovation@janelia.hhmi.org.
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FLInChR Use
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Contact

Michael Perham
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