Impact of mRNA chemistry and manufacturing process on innate immune activation.
Autorzy:
Nelson J; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Sorensen EW; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Mintri S; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Rabideau AE; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Zheng W; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Besin G; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Khatwani N; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Su SV; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Miracco EJ; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Issa WJ; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Hoge S; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. StantonMG; Moderna Inc., 200 Technology Square, Cambridge, MA, USA. Joyal JL; Moderna Inc., 200 Technology Square, Cambridge, MA, USA.
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Źródło:
Science advances [Sci Adv] 2020 Jun 24; Vol. 6 (26), pp. eaaz6893. Date of Electronic Publication: 2020 Jun 24 (Print Publication: 2020).
Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines.
Autorzy:
Hassett KJ; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Benenato KE; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Jacquinet E; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Lee A; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Woods A; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Yuzhakov O; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Himansu S; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Deterling J; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Geilich BM; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Ketova T; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Mihai C; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Lynn A; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. McFadyen I; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Moore MJ; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Senn JJ; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. StantonMG; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Almarsson Ö; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Ciaramella G; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Brito LA; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Electronic address: .
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Źródło:
Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2019 Apr 15; Vol. 15, pp. 1-11. Date of Electronic Publication: 2019 Feb 07.
A Novel Amino Lipid Series for mRNA Delivery: Improved Endosomal Escape and Sustained Pharmacology and Safety in Non-human Primates.
Autorzy:
Sabnis S; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Kumarasinghe ES; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Salerno T; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Mihai C; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Ketova T; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Senn JJ; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Lynn A; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Bulychev A; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. McFadyen I; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Chan J; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Almarsson Ö; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. StantonMG; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Benenato KE; Moderna Therapeutics, 200 Technology Square, Cambridge, MA 02139, USA. Electronic address: .
Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors.
Autorzy:
Katz JD; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: jason_. Haidle A; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Childers KK; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Zabierek AA; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Jewell JP; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Hou Y; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Altman MD; Department of Structural Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Szewczak A; Department of In Vitro Sciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Chen D; Department of Drug Metabolism, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Harsch A; Department of Drug Metabolism, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Hayashi M; Department of Neuroscience, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Warren L; Department of Neuroscience, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Hutton M; Department of Neuroscience, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Nuthall H; Department of Neuroscience, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Su HP; Department of Structural Chemistry, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA. Munshi S; Department of Structural Chemistry, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA. StantonMG; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Davies IW; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Munoz B; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Northrup A; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA.
MARK inhibitors: Declaring a No-Go decision on a chemical series based on extensive DMPK experimentation.
Autorzy:
Haidle AM; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Childers KK; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Zabierek AA; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Katz JD; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Jewell JP; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Hou Y; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Altman MD; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Szewczak A; Department of In Vitro Sciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Chen D; Department of Drug Metabolism, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Harsch A; Department of Drug Metabolism, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Hayashi M; Department of Neuroscience, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Warren L; Department of Neuroscience, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Hutton M; Department of Neuroscience, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Nuthall H; Department of Neuroscience, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. StantonMG; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Davies IW; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Munoz B; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Northrup A; Department of Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115, USA.
Systematic chemical modifications of single stranded siRNAs significantly improved CTNNB1 mRNA silencing.
Autorzy:
Chang W; Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, United States. Electronic address: . Pei Y; RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States. Guidry EN; Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, United States. Zewge D; Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, United States. Parish CA; Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, United States. Sherer EC; Structural Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, United States. DiMuzio J; RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States. Zhang H; RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States. South VJ; RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States. Strapps WR; RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States. Sepp-Lorenzino L; RNA Biology, Merck Research Laboratories, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States. Colletti SL; Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, United States. StantonMG; Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, United States.
Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties.
Autorzy:
Sloman DL; Discovery Chemistry, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Noucti N; Discovery Chemistry, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Altman MD; Chemistry Modeling and Informatics, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Chen D; Drug Metabolism and Pharmacokinetics, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Mislak AC; Drug Metabolism and Pharmacokinetics, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Szewczak A; CNS Pharmacology, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Hayashi M; CNS Pharmacology, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Warren L; CNS Pharmacology, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Dellovade T; Core Pharmacology, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Wu Z; Core Pharmacology, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Marcus J; Neuroscience Drug Discovery, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Walker D; Pharmaceutical Research and Development, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Su HP; Structural Biology, 770 Sumneytown Pike, West Point, PA 19486, United States. Edavettal SC; Structural Biology, 770 Sumneytown Pike, West Point, PA 19486, United States. Munshi S; Structural Biology, 770 Sumneytown Pike, West Point, PA 19486, United States. Hutton M; Neuroscience Drug Discovery, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. Nuthall H; Neuroscience Drug Discovery, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States. StantonMG; Discovery Chemistry, Merck and Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02215, United States.
5'-(E)-Vinylphosphonate: A Stable Phosphate Mimic Can Improve the RNAi Activity of siRNA-GalNAc Conjugates.
Autorzy:
Parmar R; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Willoughby JL; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Liu J; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Foster DJ; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Brigham B; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Theile CS; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Charisse K; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Akinc A; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Guidry E; Merck and Co., Inc, 770 Sumneytown Pike, West Point, PA, 19486, USA. Pei Y; Merck and Co., Inc, 770 Sumneytown Pike, West Point, PA, 19486, USA. Strapps W; Merck and Co., Inc, 770 Sumneytown Pike, West Point, PA, 19486, USA. Cancilla M; Merck and Co., Inc, 770 Sumneytown Pike, West Point, PA, 19486, USA. StantonMG; Merck and Co., Inc, 770 Sumneytown Pike, West Point, PA, 19486, USA. Rajeev KG; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Sepp-Lorenzino L; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Manoharan M; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Meyers R; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Maier MA; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. Jadhav V; Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA. .
Delayed and Prolonged Histone Hyperacetylation with a Selective HDAC1/HDAC2 Inhibitor.
Autorzy:
Methot JL; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Hoffman DM; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Witter DJ; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. StantonMG; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Harrington P; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Hamblett C; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Siliphaivanh P; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Wilson K; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Hubbs J; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Heidebrecht R; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Kral AM; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Ozerova N; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Fleming JC; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Wang H; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Szewczak AA; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Middleton RE; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Hughes B; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Cruz JC; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Haines BB; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Chenard M; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Kenific CM; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Harsch A; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Secrist JP; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States. Miller TA; Merck Research Laboratories , 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
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Źródło:
ACS medicinal chemistry letters [ACS Med Chem Lett] 2014 Jan 02; Vol. 5 (4), pp. 340-5. Date of Electronic Publication: 2014 Jan 02 (Print Publication: 2014).
StantonMG; Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486, USA. matthew_stanton@merck.com Colletti SL
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Źródło:
Journal of medicinal chemistry [J Med Chem] 2010 Nov 25; Vol. 53 (22), pp. 7887-901. Date of Electronic Publication: 2010 Aug 31.
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