A New Highly Efficient Molecule for Both Optogenetic and Chemogenetic Control Driven by FRET Amplification of BioLuminescence. Bjorefeldt, A., Murphy, J., Crespo, E. L., Lambert, G. G., Prakash, M., Ikefuama, E. C., Friedman, N., Brown, T. M., Lipscombe, D., Moore, C. I., Hochgeschwender, U., & Shaner, N. C. December, 2023. Journal Abbreviation: bioRxiv Pages: 2023.06.26.545546 Publication Title: bioRxiv : the preprint server for biologydoi abstract bibtex SIGNIFICANCE: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). AIM: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. APPROACH: We developed novel luciferases optimized for Forster resonance energy transfer (FRET) when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). RESULTS: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard), and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. CONCLUSIONS: We report a robust new option for achieving multiple modes of control in a single actuator, and a promising engineering strategy for continued improvement of BL-OG.
@misc{bjorefeldt_new_2023,
address = {United States},
title = {A {New} {Highly} {Efficient} {Molecule} for {Both} {Optogenetic} and {Chemogenetic} {Control} {Driven} by {FRET} {Amplification} of {BioLuminescence}.},
doi = {10.1101/2023.06.26.545546},
abstract = {SIGNIFICANCE: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). AIM: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. APPROACH: We developed novel luciferases optimized for Forster resonance energy transfer (FRET) when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). RESULTS: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard), and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. CONCLUSIONS: We report a robust new option for achieving multiple modes of control in a single actuator, and a promising engineering strategy for continued improvement of BL-OG.},
language = {eng},
author = {Bjorefeldt, Andreas and Murphy, Jeremy and Crespo, Emmanuel L. and Lambert, Gerard G. and Prakash, Mansi and Ikefuama, Ebenezer C. and Friedman, Nina and Brown, Tariq M. and Lipscombe, Diane and Moore, Christopher I. and Hochgeschwender, Ute and Shaner, Nathan C.},
month = dec,
year = {2023},
pmid = {37425735},
pmcid = {PMC10327108},
note = {Journal Abbreviation: bioRxiv
Pages: 2023.06.26.545546
Publication Title: bioRxiv : the preprint server for biology},
}
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AIM: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. APPROACH: We developed novel luciferases optimized for Forster resonance energy transfer (FRET) when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). RESULTS: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard), and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. CONCLUSIONS: We report a robust new option for achieving multiple modes of control in a single actuator, and a promising engineering strategy for continued improvement of BL-OG.","language":"eng","author":[{"propositions":[],"lastnames":["Bjorefeldt"],"firstnames":["Andreas"],"suffixes":[]},{"propositions":[],"lastnames":["Murphy"],"firstnames":["Jeremy"],"suffixes":[]},{"propositions":[],"lastnames":["Crespo"],"firstnames":["Emmanuel","L."],"suffixes":[]},{"propositions":[],"lastnames":["Lambert"],"firstnames":["Gerard","G."],"suffixes":[]},{"propositions":[],"lastnames":["Prakash"],"firstnames":["Mansi"],"suffixes":[]},{"propositions":[],"lastnames":["Ikefuama"],"firstnames":["Ebenezer","C."],"suffixes":[]},{"propositions":[],"lastnames":["Friedman"],"firstnames":["Nina"],"suffixes":[]},{"propositions":[],"lastnames":["Brown"],"firstnames":["Tariq","M."],"suffixes":[]},{"propositions":[],"lastnames":["Lipscombe"],"firstnames":["Diane"],"suffixes":[]},{"propositions":[],"lastnames":["Moore"],"firstnames":["Christopher","I."],"suffixes":[]},{"propositions":[],"lastnames":["Hochgeschwender"],"firstnames":["Ute"],"suffixes":[]},{"propositions":[],"lastnames":["Shaner"],"firstnames":["Nathan","C."],"suffixes":[]}],"month":"December","year":"2023","pmid":"37425735","pmcid":"PMC10327108","note":"Journal Abbreviation: bioRxiv Pages: 2023.06.26.545546 Publication Title: bioRxiv : the preprint server for biology","bibtex":"@misc{bjorefeldt_new_2023,\n\taddress = {United States},\n\ttitle = {A {New} {Highly} {Efficient} {Molecule} for {Both} {Optogenetic} and {Chemogenetic} {Control} {Driven} by {FRET} {Amplification} of {BioLuminescence}.},\n\tdoi = {10.1101/2023.06.26.545546},\n\tabstract = {SIGNIFICANCE: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). AIM: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. APPROACH: We developed novel luciferases optimized for Forster resonance energy transfer (FRET) when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). RESULTS: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard), and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. 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