Search Results - "Schlegel, Mark"

Acyclic ( S )-glycol nucleic acid ( S -GNA) modification of siRNAs improves the safety of RNAi therapeutics while maintaining potency by Egli, Martin, Schlegel, Mark K, Manoharan, Muthiah

“…Glycol nucleic acid (GNA) is an acyclic nucleic acid analog connected via phosphodiester bonds. Crystal structures of RNA-GNA chimeric duplexes indicated that…”
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Advanced siRNA Designs Further Improve In Vivo Performance of GalNAc-siRNA Conjugates by Foster, Donald J., Brown, Christopher R., Shaikh, Sarfraz, Trapp, Casey, Schlegel, Mark K., Qian, Kun, Sehgal, Alfica, Rajeev, Kallanthottathil G., Jadhav, Vasant, Manoharan, Muthiah, Kuchimanchi, Satya, Maier, Martin A., Milstein, Stuart

“…Significant progress has been made in the advancement of RNAi therapeutics by combining a synthetic triantennary N-acetylgalactosamine ligand targeting the…”
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Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity by Janas, Maja M., Schlegel, Mark K., Harbison, Carole E., Yilmaz, Vedat O., Jiang, Yongfeng, Parmar, Rubina, Zlatev, Ivan, Castoreno, Adam, Xu, Huilei, Shulga-Morskaya, Svetlana, Rajeev, Kallanthottathil G., Manoharan, Muthiah, Keirstead, Natalie D., Maier, Martin A., Jadhav, Vasant

“…Small interfering RNAs (siRNAs) conjugated to a trivalent N -acetylgalactosamine (GalNAc) ligand are being evaluated in investigational clinical studies for a…”
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Automated glycan assembly using the Glyconeer 2.1 synthesizer by Hahm, Heung Sik, Schlegel, Mark K., Hurevich, Mattan, Eller, Steffen, Schuhmacher, Frank, Hofmann, Johanna, Pagel, Kevin, Seeberger, Peter H.

“…Reliable and rapid access to defined biopolymers by automated DNA and peptide synthesis has fundamentally altered biological research and medical practice…”
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Expanding RNAi therapeutics to extrahepatic tissues with lipophilic conjugates by Brown, Kirk M., Nair, Jayaprakash K., Janas, Maja M., Anglero-Rodriguez, Yesseinia I., Dang, Lan T. H., Peng, Haiyan, Theile, Christopher S., Castellanos-Rizaldos, Elena, Brown, Christopher, Foster, Donald, Kurz, Jeffrey, Allen, Jeffrey, Maganti, Rajanikanth, Li, Jing, Matsuda, Shigeo, Stricos, Matthew, Chickering, Tyler, Jung, Michelle, Wassarman, Kelly, Rollins, Jeff, Woods, Lauren, Kelin, Alex, Guenther, Dale C., Mobley, Melissa W., Petrulis, John, McDougall, Robin, Racie, Timothy, Bombardier, Jessica, Cha, Diana, Agarwal, Saket, Johnson, Lei, Jiang, Yongfeng, Lentini, Scott, Gilbert, Jason, Nguyen, Tuyen, Chigas, Samantha, LeBlanc, Sarah, Poreci, Urjana, Kasper, Anne, Rogers, Arlin B., Chong, Saeho, Davis, Wendell, Sutherland, Jessica E., Castoreno, Adam, Milstein, Stuart, Schlegel, Mark K., Zlatev, Ivan, Charisse, Klaus, Keating, Mark, Manoharan, Muthiah, Fitzgerald, Kevin, Wu, Jing-Tao, Maier, Martin A., Jadhav, Vasant

“…Therapeutics based on short interfering RNAs (siRNAs) delivered to hepatocytes have been approved, but new delivery solutions are needed to target additional…”
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siRNAs containing 2′-fluorinated Northern-methanocarbacyclic (2′-F-NMC) nucleotides: in vitro and in vivo RNAi activity and inability of mitochondrial polymerases to incorporate 2′-F-NMC NTPs by Akabane-Nakata, Masaaki, Erande, Namrata D, Kumar, Pawan, Degaonkar, Rohan, Gilbert, Jason A, Qin, June, Mendez, Martha, Woods, Lauren Blair, Jiang, Yongfeng, Janas, Maja M, O’Flaherty, Derek K, Zlatev, Ivan, Schlegel, Mark K, Matsuda, Shigeo, Egli, Martin, Manoharan, Muthiah

“…Abstract We recently reported the synthesis of 2′-fluorinated Northern-methanocarbacyclic (2′-F-NMC) nucleotides, which are based on a bicyclo[3.1.0]hexane…”
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Reversal of siRNA-mediated gene silencing in vivo by Zlatev, Ivan, Castoreno, Adam, Brown, Christopher R, Qin, June, Waldron, Scott, Schlegel, Mark K, Degaonkar, Rohan, Shulga-Morskaya, Svetlana, Xu, Huilei, Gupta, Swati, Matsuda, Shigeo, Akinc, Akin, Rajeev, Kallanthottathil G, Manoharan, Muthiah, Maier, Martin A, Jadhav, Vasant

“…Gene silencing by siRNAs in vivo is reversed using sequence-specific high-affinity oligonucleotides. We report rapid, potent reversal of GalNAc-siRNA-mediated…”
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Synthesis, chirality-dependent conformational and biological properties of siRNAs containing 5′-(R)- and 5′-(S)-C-methyl-guanosine by Mikami, Atsushi, Erande, Namrata, Matsuda, Shigeo, Kel’in, Alexander, Woods, Lauren Blair, Chickering, Tyler, Pallan, Pradeep S, Schlegel, Mark K, Zlatev, Ivan, Egli, Martin, Manoharan, Muthiah

“…Abstract Various chemical modifications have been identified that enhance potency of small interfering RNAs (siRNAs) and that reduce off-target effects, immune…”
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RNAs Containing Carbocyclic Ribonucleotides by Akabane-Nakata, Masaaki, Chickering, Tyler, Harp, Joel M, Schlegel, Mark K, Matsuda, Shigeo, Egli, Martin, Manoharan, Muthiah

“…Toward the goal of evaluation of carbocyclic ribonucleoside-containing oligonucleotide therapeutics, we developed convenient, scalable syntheses of all four…”
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Chirality Dependent Potency Enhancement and Structural Impact of Glycol Nucleic Acid Modification on siRNA by Schlegel, Mark K, Foster, Donald J, Kel’in, Alexander V, Zlatev, Ivan, Bisbe, Anna, Jayaraman, Muthusamy, Lackey, Jeremy G, Rajeev, Kallanthottathil G, Charissé, Klaus, Harp, Joel, Pallan, Pradeep S, Maier, Martin A, Egli, Martin, Manoharan, Muthiah

“…Here we report the investigation of glycol nucleic acid (GNA), an acyclic nucleic acid analogue, as a modification of siRNA duplexes. We evaluated the impact…”
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From bench to bedside: Improving the clinical safety of GalNAc–siRNA conjugates using seed-pairing destabilization by Schlegel, Mark K, Janas, Maja M, Jiang, Yongfeng, Barry, Joseph D, Davis, Wendell, Agarwal, Saket, Berman, Daniel, Brown, Christopher R, Castoreno, Adam, LeBlanc, Sarah, Liebow, Abigail, Mayo, Tara, Milstein, Stuart, Nguyen, Tuyen, Shulga-Morskaya, Svetlana, Hyde, Sarah, Schofield, Sally, Szeto, John, Woods, Lauren Blair, Yilmaz, Vedat O, Manoharan, Muthiah, Egli, Martin, Charissé, Klaus, Sepp-Lorenzino, Laura, Haslett, Patrick, Fitzgerald, Kevin, Jadhav, Vasant, Maier, Martin A

“…Abstract Preclinical mechanistic studies have pointed towards RNA interference-mediated off-target effects as a major driver of hepatotoxicity for GalNAc–siRNA…”
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Duplex Structure of a Minimal Nucleic Acid by Schlegel, Mark K, Essen, Lars-Oliver, Meggers, Eric

“…The crystal structure of an 8-mer (S)-GNA duplex is presented. As a tool for phasing, the anomalous diffraction of two copper(II) ions within two artificial…”
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Safety evaluation of 2′-deoxy-2′-fluoro nucleotides in GalNAc-siRNA conjugates by Janas, Maja M, Zlatev, Ivan, Liu, Ju, Jiang, Yongfeng, Barros, Scott A, Sutherland, Jessica E, Davis, Wendell P, Liu, Jingxuan, Brown, Christopher R, Liu, Xiumin, Schlegel, Mark K, Blair, Lauren, Zhang, Xuemei, Das, Biplab, Tran, Chris, Aluri, Krishna, Li, Jing, Agarwal, Saket, Indrakanti, Ramesh, Charisse, Klaus, Nair, Jayaprakash, Matsuda, Shigeo, Rajeev, Kallanthottathil G, Zimmermann, Tracy, Sepp-Lorenzino, Laura, Xu, Yuanxin, Akinc, Akin, Fitzgerald, Kevin, Vaishnaw, Akshay K, Smith, Peter F, Manoharan, Muthiah, Jadhav, Vasant, Wu, Jing-Tao, Maier, Martin A

“…Abstract For oligonucleotide therapeutics, chemical modifications of the sugar-phosphate backbone are frequently used to confer drug-like properties. Because…”
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A platform to screen for C-type lectin receptor-binding carbohydrates and their potential for cell-specific targeting and immune modulation by Maglinao, Maha, Eriksson, Magdalena, Schlegel, Mark K., Zimmermann, Stephanie, Johannssen, Timo, Götze, Sebastian, Seeberger, Peter H., Lepenies, Bernd

“…Myeloid C-type lectin receptors (CLRs) in innate immunity represent a superfamily of pattern recognition receptors that recognize carbohydrate structures on…”
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Chimeric siRNAs with chemically modified pentofuranose and hexopyranose nucleotides: altritol-nucleotide (ANA) containing GalNAc-siRNA conjugates: in vitro and in vivo RNAi activity and resistance to 5'-exonuclease by Kumar, Pawan, Degaonkar, Rohan, Guenther, Dale C, Abramov, Mikhail, Schepers, Guy, Capobianco, Marie, Jiang, Yongfeng, Harp, Joel, Kaittanis, Charalambos, Janas, Maja M, Castoreno, Adam, Zlatev, Ivan, Schlegel, Mark K, Herdewijn, Piet, Egli, Martin, Manoharan, Muthiah

“…In this report, we investigated the hexopyranose chemical modification Altriol Nucleic Acid (ANA) within small interfering RNA (siRNA) duplexes that were…”
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Overcoming GNA/RNA base-pairing limitations using isonucleotides improves the pharmacodynamic activity of ESC+ GalNAc-siRNAs by Schlegel, Mark K, Matsuda, Shigeo, Brown, Christopher R, Harp, Joel M, Barry, Joseph D, Berman, Daniel, Castoreno, Adam, Schofield, Sally, Szeto, John, Manoharan, Muthiah, Charissé, Klaus, Egli, Martin, Maier, Martin A

“…Abstract We recently reported that RNAi-mediated off-target effects are important drivers of the hepatotoxicity observed for a subset of GalNAc–siRNA…”
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RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes by Subramanian, Megha, McIninch, James, Zlatev, Ivan, Schlegel, Mark K., Kaittanis, Charalambos, Nguyen, Tuyen, Agarwal, Saket, Racie, Timothy, Alvarado, Martha Arbaiza, Wassarman, Kelly, Collins, Thomas S., Chickering, Tyler, Brown, Christopher R., Schmidt, Karyn, Castoreno, Adam B., Shulga-Morskaya, Svetlana, Stamenova, Elena, Buckowing, Kira, Berman, Daniel, Barry, Joseph D., Bisbe, Anna, Maier, Martin A., Fitzgerald, Kevin, Jadhav, Vasant

“…Adeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression…”
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Incorporating a Thiophosphate Modification into a Common RNA Tetraloop Motif Causes an Unanticipated Stability Boost by Pallan, Pradeep S, Lybrand, Terry P, Schlegel, Mark K, Harp, Joel M, Jahns, Hartmut, Manoharan, Muthiah, Egli, Martin

“…GNRA (N = A, C, G, or U; R = A or G) tetraloops are common RNA secondary structural motifs and feature a phosphate stacked atop a nucleobase. The rRNA…”
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Shorter Is Better: The α‑(l)‑Threofuranosyl Nucleic Acid Modification Improves Stability, Potency, Safety, and Ago2 Binding and Mitigates Off-Target Effects of Small Interfering RNAs by Matsuda, Shigeo, Bala, Saikat, Liao, Jen-Yu, Datta, Dhrubajyoti, Mikami, Atsushi, Woods, Lauren, Harp, Joel M., Gilbert, Jason A., Bisbe, Anna, Manoharan, Rajar M., Kim, MaryBeth, Theile, Christopher S., Guenther, Dale C., Jiang, Yongfeng, Agarwal, Saket, Maganti, Rajanikanth, Schlegel, Mark K., Zlatev, Ivan, Charisse, Klaus, Rajeev, Kallanthottathil G., Castoreno, Adam, Maier, Martin, Janas, Maja M., Egli, Martin, Chaput, John C., Manoharan, Muthiah

“…Chemical modifications are necessary to ensure the metabolic stability and efficacy of oligonucleotide-based therapeutics. Here, we describe analyses of the…”
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Impact of Oligonucleotide Structure, Chemistry, and Delivery Method on In Vitro Cytotoxicity by Janas, Maja M, Jiang, Yongfeng, Schlegel, Mark K, Waldron, Scott, Kuchimanchi, Satya, Barros, Scott A

“…Single-stranded (ss) 2'-fluoro (2'-F)-modified oligonucleotides (ONs) with a full phosphorothioate (PS) backbone have been reported to be cytotoxic and cause…”
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