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The nucleobase guanine at the 3'-terminus of oligonucleotide RGLS4326 drives off-target AMPAR inhibition and CNS toxicity.

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Title: The nucleobase guanine at the 3'-terminus of oligonucleotide RGLS4326 drives off-target AMPAR inhibition and CNS toxicity.
Authors: Valencia T; Regulus Therapeutics Inc., San Diego, CA, USA., Yen LY; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.; Cellular and Molecular Physiology and Biophysics Graduate Program, Columbia University Irving Medical Center, New York, NY, USA., Berman C; Berman Consulting, Wayland, MA, USA., Vincent T; Regulus Therapeutics Inc., San Diego, CA, USA., Davis S; Regulus Therapeutics Inc., San Diego, CA, USA., Varrone F; Regulus Therapeutics Inc., San Diego, CA, USA., Huang J; Regulus Therapeutics Inc., San Diego, CA, USA., Mastroianni J; Regulus Therapeutics Inc., San Diego, CA, USA., Carlson M; Regulus Therapeutics Inc., San Diego, CA, USA., Owen T; Regulus Therapeutics Inc., San Diego, CA, USA., Kamel A; Regulus Therapeutics Inc., San Diego, CA, USA., Drygin D; Regulus Therapeutics Inc., San Diego, CA, USA., Kinberger GA; Regulus Therapeutics Inc., San Diego, CA, USA., Gangwar SP; Cellular and Molecular Physiology and Biophysics Graduate Program, Columbia University Irving Medical Center, New York, NY, USA., Yelshanskaya MV; Cellular and Molecular Physiology and Biophysics Graduate Program, Columbia University Irving Medical Center, New York, NY, USA., Ridley J; Metrion Biosciences Ltd, Granta Park, Cambridge, UK., Kirby R; Metrion Biosciences Ltd, Granta Park, Cambridge, UK., Alvarez J; Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Lakhia R; Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Patel V; Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Sobolevsky AI; Cellular and Molecular Physiology and Biophysics Graduate Program, Columbia University Irving Medical Center, New York, NY, USA. as4005@cumc.columbia.edu., Lee EC; Regulus Therapeutics Inc., San Diego, CA, USA. elee@regulusrx.com.
Source: Nature communications [Nat Commun] 2025 Nov 28; Vol. 16 (1), pp. 10762. Date of Electronic Publication: 2025 Nov 28.
Publication Type: Journal Article
Journal Info: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Database: MEDLINE Ultimate
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  Data: The nucleobase guanine at the 3'-terminus of oligonucleotide RGLS4326 drives off-target AMPAR inhibition and CNS toxicity.
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  Data: <searchLink fieldCode="AU" term="%22Valencia+T%22">Valencia T</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Yen+LY%22">Yen LY</searchLink>; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.; Cellular and Molecular Physiology and Biophysics Graduate Program, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Berman+C%22">Berman C</searchLink>; Berman Consulting, Wayland, MA, USA.<br /><searchLink fieldCode="AU" term="%22Vincent+T%22">Vincent T</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Davis+S%22">Davis S</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Varrone+F%22">Varrone F</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Huang+J%22">Huang J</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Mastroianni+J%22">Mastroianni J</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Carlson+M%22">Carlson M</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Owen+T%22">Owen T</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Kamel+A%22">Kamel A</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Drygin+D%22">Drygin D</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Kinberger+GA%22">Kinberger GA</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA.<br /><searchLink fieldCode="AU" term="%22Gangwar+SP%22">Gangwar SP</searchLink>; Cellular and Molecular Physiology and Biophysics Graduate Program, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Yelshanskaya+MV%22">Yelshanskaya MV</searchLink>; Cellular and Molecular Physiology and Biophysics Graduate Program, Columbia University Irving Medical Center, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Ridley+J%22">Ridley J</searchLink>; Metrion Biosciences Ltd, Granta Park, Cambridge, UK.<br /><searchLink fieldCode="AU" term="%22Kirby+R%22">Kirby R</searchLink>; Metrion Biosciences Ltd, Granta Park, Cambridge, UK.<br /><searchLink fieldCode="AU" term="%22Alvarez+J%22">Alvarez J</searchLink>; Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA.<br /><searchLink fieldCode="AU" term="%22Lakhia+R%22">Lakhia R</searchLink>; Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA.<br /><searchLink fieldCode="AU" term="%22Patel+V%22">Patel V</searchLink>; Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA.<br /><searchLink fieldCode="AU" term="%22Sobolevsky+AI%22">Sobolevsky AI</searchLink>; Cellular and Molecular Physiology and Biophysics Graduate Program, Columbia University Irving Medical Center, New York, NY, USA. as4005@cumc.columbia.edu.<br /><searchLink fieldCode="AU" term="%22Lee+EC%22">Lee EC</searchLink>; Regulus Therapeutics Inc., San Diego, CA, USA. elee@regulusrx.com.
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