Investigating the pharmacodynamic durability of GalNAc-siRNA conjugates.

Autor: Brown CR; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Gupta S; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Qin J; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Racie T; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., He G; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Lentini S; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Malone R; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Yu M; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Matsuda S; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Shulga-Morskaya S; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Nair AV; MGH Program in Membrane Biology, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Theile CS; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Schmidt K; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Shahraz A; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Goel V; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Parmar RG; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Zlatev I; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Schlegel MK; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Nair JK; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Jayaraman M; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Manoharan M; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Brown D; MGH Program in Membrane Biology, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Maier MA; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA., Jadhav V; Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA.

Publikováno v: Nucleic acids research [Nucleic Acids Res] 2020 Dec 02; Vol. 48 (21), pp. 11827-11844.

Facile Synthesis, Geometry, and 2'-Substituent-Dependent in Vivo Activity of 5'-(E)- and 5'-(Z)-Vinylphosphonate-Modified siRNA Conjugates.

Autor: Parmar RG; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Brown CR; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Matsuda S; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Willoughby JLS; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Theile CS; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Charissé K; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Foster DJ; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Zlatev I; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Jadhav V; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Maier MA; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Egli M; Department of Biochemistry and Center for Structural Biology, Vanderbilt University, School of Medicine , Nashville, Tennessee 37232, United States., Manoharan M; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States., Rajeev KG; Alnylam Pharmaceuticals , 300 Third Street, Cambridge, Massachusetts 02142, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2018 Feb 08; Vol. 61 (3), pp. 734-744. Date of Electronic Publication: 2018 Jan 27.

Development of a liver-targeted siRNA delivery platform with a broad therapeutic window utilizing biodegradable polypeptide-based polymer conjugates.

Autor: Barrett SE; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA. Electronic address: stephanie_barrett@merck.com., Burke RS; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Abrams MT; Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Bason C; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Busuek M; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Carlini E; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Carr BA; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Crocker LS; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Fan H; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Garbaccio RM; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Guidry EN; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065, USA., Heo JH; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Howell BJ; Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Kemp EA; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Kowtoniuk RA; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Latham AH; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Leone AM; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Lyman M; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Parmar RG; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Patel M; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Pechenov SY; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Pei T; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065, USA., Pudvah NT; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Raab C; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Riley S; Department of RNAi Analytical Sciences, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Sepp-Lorenzino L; Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Smith S; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Soli ED; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065, USA., Staskiewicz S; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065, USA., Stern M; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Truong Q; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065, USA., Vavrek M; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Waldman JH; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065, USA., Walsh ES; Department of RNA Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Williams JM; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Young S; Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA., Colletti SL; Department of RNA Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA.

Publikováno v: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2014 Jun 10; Vol. 183, pp. 124-37. Date of Electronic Publication: 2014 Mar 21.

Improving the in vivo therapeutic index of siRNA polymer conjugates through increasing pH responsiveness.

Autor: Guidry EN; Department of Process Chemistry and ∥Department of Analytical Chemistry, Merck & Co. Inc. , , Rahway, New Jersey, United States., Farand J, Soheili A, Parish CA, Kevin NJ, Pipik B, Calati KB, Ikemoto N, Waldman JH, Latham AH, Howell BJ, Leone A, Garbaccio RM, Barrett SE, Parmar RG, Truong QT, Mao B, Davies IW, Colletti SL, Sepp-Lorenzino L

Publikováno v: Bioconjugate chemistry [Bioconjug Chem] 2014 Feb 19; Vol. 25 (2), pp. 296-307. Date of Electronic Publication: 2014 Jan 10.