Chemical modification of PS-ASO therapeutics reduces cellular protein-binding and improves the therapeutic index

[1]  KasuyaTakeshi,et al.  Role of Computationally Evaluated Target Specificity in the Hepatotoxicity of Gapmer Antisense Oligonucleotides. , 2018 .

[2]  T. Abe,et al.  Loss of Sfpq Causes Long-Gene Transcriptopathy in the Brain. , 2018, Cell reports.

[3]  S. Crooke,et al.  Cellular uptake mediated by epidermal growth factor receptor facilitates the intracellular activity of phosphorothioate-modified antisense oligonucleotides , 2018, Nucleic acids research.

[4]  S. Crooke,et al.  Acute hepatotoxicity of 2′ fluoro-modified 5–10–5 gapmer phosphorothioate oligonucleotides in mice correlates with intracellular protein binding and the loss of DBHS proteins , 2018, Nucleic acids research.

[5]  Howard Y. Chang,et al.  Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders , 2018, Nature.

[6]  T. Singer,et al.  A Sensitive In Vitro Approach to Assess the Hybridization-Dependent Toxic Potential of High Affinity Gapmer Oligonucleotides , 2017, Molecular therapy. Nucleic acids.

[7]  S. Crooke,et al.  Nucleic acid binding proteins affect the subcellular distribution of phosphorothioate antisense oligonucleotides , 2017, Nucleic acids research.

[8]  S. Crooke,et al.  Dynamic nucleoplasmic and nucleolar localization of mammalian RNase H1 in response to RNAP I transcriptional R-loops , 2017, Nucleic acids research.

[9]  T. Gant,et al.  Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs , 2017, Molecular therapy. Nucleic acids.

[10]  S. Crooke,et al.  RNase H1-Dependent Antisense Oligonucleotides Are Robustly Active in Directing RNA Cleavage in Both the Cytoplasm and the Nucleus , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[11]  H. Bohr,et al.  Electronic Structures of LNA Phosphorothioate Oligonucleotides , 2017, Molecular therapy. Nucleic acids.

[12]  T. CrookeStanley Molecular Mechanisms of Antisense Oligonucleotides. , 2017 .

[13]  S. Crooke,et al.  Depletion of NEAT1 lncRNA attenuates nucleolar stress by releasing sequestered P54nrb and PSF to facilitate c-Myc translation , 2017, PloS one.

[14]  Stanley T Crooke,et al.  Cellular uptake and trafficking of antisense oligonucleotides , 2017, Nature Biotechnology.

[15]  anastasia. khvorova,et al.  The chemical evolution of oligonucleotide therapies of clinical utility , 2017, Nature Biotechnology.

[16]  S. Crooke,et al.  Development of a Quantitative BRET Affinity Assay for Nucleic Acid-Protein Interactions , 2016, PloS one.

[17]  T. Kasuya,et al.  Ribonuclease H1-dependent hepatotoxicity caused by locked nucleic acid-modified gapmer antisense oligonucleotides , 2016, Scientific Reports.

[18]  T. Singer,et al.  Establishment of a Predictive In Vitro Assay for Assessment of the Hepatotoxic Potential of Oligonucleotide Drugs , 2016, PloS one.

[19]  Christopher E. Hart,et al.  Viable RNaseH1 knockout mice show RNaseH1 is essential for R loop processing, mitochondrial and liver function , 2016, Nucleic acids research.

[20]  A. Ryan,et al.  Development of a Method for Profiling Protein Interactions with LNA-Modified Antisense Oligonucleotides Using Protein Microarrays. , 2016, Nucleic acid therapeutics.

[21]  S. Crooke,et al.  Hsp90 protein interacts with phosphorothioate oligonucleotides containing hydrophobic 2′-modifications and enhances antisense activity , 2016, Nucleic acids research.

[22]  Christopher E. Hart,et al.  Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts , 2015, Nucleic acids research.

[23]  Steven A. Brown,et al.  Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects , 2015, Nature Neuroscience.

[24]  Emma L. Koppe,et al.  In silico and in vitro evaluation of exonic and intronic off-target effects form a critical element of therapeutic ASO gapmer optimization , 2015, Nucleic acids research.

[25]  S. Crooke,et al.  The rates of the major steps in the molecular mechanism of RNase H1-dependent antisense oligonucleotide induced degradation of RNA , 2015, Nucleic acids research.

[26]  T. P. Prakash,et al.  Efficient Synthesis and Biological Evaluation of 5'-GalNAc Conjugated Antisense Oligonucleotides. , 2015, Bioconjugate chemistry.

[27]  J. Lieberman,et al.  Apoptosis Triggers Specific, Rapid, and Global mRNA Decay with 3′ Uridylated Intermediates Degraded by DIS3L2 , 2015, Cell reports.

[28]  S. Crooke,et al.  2′-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF , 2015, Nucleic acids research.

[29]  S. Crooke,et al.  Identification and characterization of intracellular proteins that bind oligonucleotides with phosphorothioate linkages , 2022 .

[30]  Kendall S. Frazier,et al.  Antisense Oligonucleotide Therapies , 2015, Toxicologic pathology.

[31]  S. Crooke,et al.  Phosphorothioate oligonucleotides can displace NEAT1 RNA and form nuclear paraspeckle-like structures , 2014, Nucleic acids research.

[32]  S. Crooke,et al.  TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co-localize in oligonucleotide-induced nuclear bodies in mammalian cells , 2014, Nucleic acids research.

[33]  H. Bohr,et al.  Quantum mechanical studies of DNA and LNA. , 2014, Nucleic acid therapeutics.

[34]  A. Burdick,et al.  Comparison of hepatic transcription profiles of locked ribonucleic acid antisense oligonucleotides: evidence of distinct pathways contributing to non-target mediated toxicity in mice. , 2014, Toxicological sciences : an official journal of the Society of Toxicology.

[35]  A. Burdick,et al.  Sequence motifs associated with hepatotoxicity of locked nucleic acid—modified antisense oligonucleotides , 2014, Nucleic acids research.

[36]  M. Lindow,et al.  Hepatotoxic potential of therapeutic oligonucleotides can be predicted from their sequence and modification pattern. , 2013, Nucleic acid therapeutics.

[37]  Stormy J. Chamberlain,et al.  Topoisomerases facilitate transcription of long genes linked to autism , 2013, Nature.

[38]  S. Crooke,et al.  Human RNase H1 Is Associated with Protein P32 and Is Involved in Mitochondrial Pre-rRNA Processing , 2013, PloS one.

[39]  J. Kreeger,et al.  Chemical modification study of antisense gapmers. , 2012, Nucleic acid therapeutics.

[40]  Stephanie C Huelga,et al.  Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs , 2012, Nature Neuroscience.

[41]  Gene W. Yeo,et al.  Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43 , 2011, Nature Neuroscience.

[42]  E. Swayze,et al.  The Medicinal Chemistry of Oligonucleotides , 2008 .

[43]  B. Monia,et al.  Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals , 2006, Nucleic acids research.

[44]  S. Crooke,et al.  Determination of the Role of the Human RNase H1 in the Pharmacology of DNA-like Antisense Drugs* , 2004, Journal of Biological Chemistry.

[45]  Y. Shav-Tal,et al.  PSF and p54nrb/NonO – multi‐functional nuclear proteins , 2002, FEBS letters.

[46]  D. Spector,et al.  Phosphorothioate antisense oligonucleotides induce the formation of nuclear bodies. , 1998, Molecular biology of the cell.

[47]  M. Nerenberg,et al.  Effect of phosphorothioate modification of oligodeoxynucleotides on specific protein binding. , 1994, The Journal of biological chemistry.

[48]  Y. Cheng,et al.  Phosphorothioate oligonucleotides are inhibitors of human DNA polymerases and RNase H: implications for antisense technology. , 1992, Molecular pharmacology.

[49]  D. Schlessinger,et al.  Differences in rRNA metabolism of primary and SV40-transformed human fibroblasts , 1978, Cell.