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RNA-Targeted Therapeutics.

Crooke ST, Witztum JL, Bennett CF, Baker BF.

Cell Metab. 2018 Apr 3;27(4):714-739. doi: 10.1016/j.cmet.2018.03.004. Review.


Cellular uptake mediated by epidermal growth factor receptor facilitates the intracellular activity of phosphorothioate-modified antisense oligonucleotides.

Wang S, Allen N, Vickers TA, Revenko AS, Sun H, Liang XH, Crooke ST.

Nucleic Acids Res. 2018 Apr 20;46(7):3579-3594. doi: 10.1093/nar/gky145.


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.

Shen W, De Hoyos CL, Sun H, Vickers TA, Liang XH, Crooke ST.

Nucleic Acids Res. 2018 Mar 16;46(5):2204-2217. doi: 10.1093/nar/gky060.


The Effects of 2'-O-Methoxyethyl Oligonucleotides on Renal Function in Humans.

Crooke ST, Baker BF, Pham NC, Hughes SG, Kwoh TJ, Cai D, Tsimikas S, Geary RS, Bhanot S.

Nucleic Acid Ther. 2018 Feb;28(1):10-22. doi: 10.1089/nat.2017.0693. Epub 2017 Nov 29.


Translation can affect the antisense activity of RNase H1-dependent oligonucleotides targeting mRNAs.

Liang XH, Nichols JG, Sun H, Crooke ST.

Nucleic Acids Res. 2018 Jan 9;46(1):293-313. doi: 10.1093/nar/gkx1174.


Dynamic nucleoplasmic and nucleolar localization of mammalian RNase H1 in response to RNAP I transcriptional R-loops.

Shen W, Sun H, De Hoyos CL, Bailey JK, Liang XH, Crooke ST.

Nucleic Acids Res. 2017 Oct 13;45(18):10672-10692. doi: 10.1093/nar/gkx710.


Nucleic acid binding proteins affect the subcellular distribution of phosphorothioate antisense oligonucleotides.

Bailey JK, Shen W, Liang XH, Crooke ST.

Nucleic Acids Res. 2017 Oct 13;45(18):10649-10671. doi: 10.1093/nar/gkx709.


Antisense oligonucleotides targeting translation inhibitory elements in 5' UTRs can selectively increase protein levels.

Liang XH, Sun H, Shen W, Wang S, Yao J, Migawa MT, Bui HH, Damle SS, Riney S, Graham MJ, Crooke RM, Crooke ST.

Nucleic Acids Res. 2017 Sep 19;45(16):9528-9546. doi: 10.1093/nar/gkx632.


RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions.

MacLeod AR, Crooke ST.

J Clin Pharmacol. 2017 Oct;57 Suppl 10:S43-S59. doi: 10.1002/jcph.957. Review.


RNase H1-Dependent Antisense Oligonucleotides Are Robustly Active in Directing RNA Cleavage in Both the Cytoplasm and the Nucleus.

Liang XH, Sun H, Nichols JG, Crooke ST.

Mol Ther. 2017 Sep 6;25(9):2075-2092. doi: 10.1016/j.ymthe.2017.06.002. Epub 2017 Jun 27.


Specific Increase of Protein Levels by Enhancing Translation Using Antisense Oligonucleotides Targeting Upstream Open Frames.

Liang XH, Shen W, Crooke ST.

Adv Exp Med Biol. 2017;983:129-146. doi: 10.1007/978-981-10-4310-9_9.


Identification of metabolically stable 5΄-phosphate analogs that support single-stranded siRNA activity.

Prakash TP, Lima WF, Murray HM, Li W, Kinberger GA, Chappell AE, Gaus H, Seth PP, Bhat B, Crooke ST, Swayze EE.

Nucleic Acids Res. 2017 Jun 20;45(11):6994. doi: 10.1093/nar/gkx381. No abstract available.


Intra-endosomal trafficking mediated by lysobisphosphatidic acid contributes to intracellular release of phosphorothioate-modified antisense oligonucleotides.

Wang S, Sun H, Tanowitz M, Liang XH, Crooke ST.

Nucleic Acids Res. 2017 May 19;45(9):5309-5322. doi: 10.1093/nar/gkx231.


Depletion of NEAT1 lncRNA attenuates nucleolar stress by releasing sequestered P54nrb and PSF to facilitate c-Myc translation.

Shen W, Liang XH, Sun H, De Hoyos CL, Crooke ST.

PLoS One. 2017 Mar 13;12(3):e0173494. doi: 10.1371/journal.pone.0173494. eCollection 2017.


Cellular uptake and trafficking of antisense oligonucleotides.

Crooke ST, Wang S, Vickers TA, Shen W, Liang XH.

Nat Biotechnol. 2017 Mar;35(3):230-237. doi: 10.1038/nbt.3779. Epub 2017 Feb 27. Review.


The Effects of 2'-O-Methoxyethyl Containing Antisense Oligonucleotides on Platelets in Human Clinical Trials.

Crooke ST, Baker BF, Witztum JL, Kwoh TJ, Pham NC, Salgado N, McEvoy BW, Cheng W, Hughes SG, Bhanot S, Geary RS.

Nucleic Acid Ther. 2017 Jun;27(3):121-129. doi: 10.1089/nat.2016.0650. Epub 2017 Feb 1.


Molecular Mechanisms of Antisense Oligonucleotides.

Crooke ST.

Nucleic Acid Ther. 2017 Apr;27(2):70-77. doi: 10.1089/nat.2016.0656. Epub 2017 Jan 12. Review.


Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials.

Viney NJ, van Capelleveen JC, Geary RS, Xia S, Tami JA, Yu RZ, Marcovina SM, Hughes SG, Graham MJ, Crooke RM, Crooke ST, Witztum JL, Stroes ES, Tsimikas S.

Lancet. 2016 Nov 5;388(10057):2239-2253. doi: 10.1016/S0140-6736(16)31009-1. Epub 2016 Sep 21.


Development of a Quantitative BRET Affinity Assay for Nucleic Acid-Protein Interactions.

Vickers TA, Crooke ST.

PLoS One. 2016 Aug 29;11(8):e0161930. doi: 10.1371/journal.pone.0161930. eCollection 2016.


Translation efficiency of mRNAs is increased by antisense oligonucleotides targeting upstream open reading frames.

Liang XH, Shen W, Sun H, Migawa MT, Vickers TA, Crooke ST.

Nat Biotechnol. 2016 Aug;34(8):875-80. doi: 10.1038/nbt.3589. Epub 2016 Jul 11.


Annexin A2 facilitates endocytic trafficking of antisense oligonucleotides.

Wang S, Sun H, Tanowitz M, Liang XH, Crooke ST.

Nucleic Acids Res. 2016 Sep 6;44(15):7314-30. doi: 10.1093/nar/gkw595. Epub 2016 Jul 4.


Integrated Safety Assessment of 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers.

Crooke ST, Baker BF, Kwoh TJ, Cheng W, Schulz DJ, Xia S, Salgado N, Bui HH, Hart CE, Burel SA, Younis HS, Geary RS, Henry SP, Bhanot S.

Mol Ther. 2016 Oct;24(10):1771-1782. doi: 10.1038/mt.2016.136. Epub 2016 Jun 30.


Viable RNaseH1 knockout mice show RNaseH1 is essential for R loop processing, mitochondrial and liver function.

Lima WF, Murray HM, Damle SS, Hart CE, Hung G, De Hoyos CL, Liang XH, Crooke ST.

Nucleic Acids Res. 2016 Jun 20;44(11):5299-312. doi: 10.1093/nar/gkw350. Epub 2016 Apr 29.


Community crystal gazing.

Acharya A, Bingham K, Bradner J, Burke W, Charo RA, Cherry J, Choulika A, Coles T, Cook-Deegan R, Crooke ST, Díaz E, Erickson B, Giddings LV, Giwa SE, Greenwood JC, Gulati V, Hall S, Harris J, Heywood J, Hill C, Levin J, Mangubat A, Maraganore J, Mariggi G, Mazur BJ, McGuire AL, Moll N, Moreno J, Naughton G, Nelsen L, Osbourn J, Perez D, Reed J, Schmidt E, Seyfert-Margolis V, Stoffels P, Thorball J, O'Toole T, Vainu I, van Deventer S, Zerhouni E, Zohar D.

Nat Biotechnol. 2016 Mar;34(3):276-83. doi: 10.1038/nbt.3515. No abstract available. Erratum in: Nat Biotechnol. 2016 Jun;34(6):666. Crook, Stanley T [Corrected to Crooke, Stanley T]. Nat Biotechnol. 2016 Jun 9;34(6):666.


Hsp90 protein interacts with phosphorothioate oligonucleotides containing hydrophobic 2'-modifications and enhances antisense activity.

Liang XH, Shen W, Sun H, Kinberger GA, Prakash TP, Nichols JG, Crooke ST.

Nucleic Acids Res. 2016 May 5;44(8):3892-907. doi: 10.1093/nar/gkw144. Epub 2016 Mar 3.


RNA cleavage products generated by antisense oligonucleotides and siRNAs are processed by the RNA surveillance machinery.

Lima WF, De Hoyos CL, Liang XH, Crooke ST.

Nucleic Acids Res. 2016 Apr 20;44(7):3351-63. doi: 10.1093/nar/gkw065. Epub 2016 Feb 3.


Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts.

Burel SA, Hart CE, Cauntay P, Hsiao J, Machemer T, Katz M, Watt A, Bui HH, Younis H, Sabripour M, Freier SM, Hung G, Dan A, Prakash TP, Seth PP, Swayze EE, Bennett CF, Crooke ST, Henry SP.

Nucleic Acids Res. 2016 Mar 18;44(5):2093-109. doi: 10.1093/nar/gkv1210. Epub 2015 Nov 8.


The rates of the major steps in the molecular mechanism of RNase H1-dependent antisense oligonucleotide induced degradation of RNA.

Vickers TA, Crooke ST.

Nucleic Acids Res. 2015 Oct 15;43(18):8955-63. doi: 10.1093/nar/gkv920. Epub 2015 Sep 17.


2'-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF.

Shen W, Liang XH, Sun H, Crooke ST.

Nucleic Acids Res. 2015 May 19;43(9):4569-78. doi: 10.1093/nar/gkv298. Epub 2015 Apr 8.


Health security preparedness and industry trends.

Crooke ST.

Health Secur. 2015 Mar-Apr;13(2):74-81. Epub 2015 Mar 16.


Efficient and selective knockdown of small non-coding RNAs.

Liang XH, Shen W, Crooke ST.

Methods Mol Biol. 2015;1296:203-11. doi: 10.1007/978-1-4939-2547-6_19.


Identification of metabolically stable 5'-phosphate analogs that support single-stranded siRNA activity.

Prakash TP, Lima WF, Murray HM, Li W, Kinberger GA, Chappell AE, Gaus H, Seth PP, Bhat B, Crooke ST, Swayze EE.

Nucleic Acids Res. 2015 Mar 31;43(6):2993-3011. doi: 10.1093/nar/gkv162. Epub 2015 Mar 9.


Identification and characterization of intracellular proteins that bind oligonucleotides with phosphorothioate linkages.

Liang XH, Sun H, Shen W, Crooke ST.

Nucleic Acids Res. 2015 Mar 11;43(5):2927-45. doi: 10.1093/nar/gkv143. Epub 2015 Feb 20.


Targeting of repeated sequences unique to a gene results in significant increases in antisense oligonucleotide potency.

Vickers TA, Freier SM, Bui HH, Watt A, Crooke ST.

PLoS One. 2014 Oct 15;9(10):e110615. doi: 10.1371/journal.pone.0110615. eCollection 2014.


Antisense oligonucleotides capable of promoting specific target mRNA reduction via competing RNase H1-dependent and independent mechanisms.

Vickers TA, Crooke ST.

PLoS One. 2014 Oct 9;9(10):e108625. doi: 10.1371/journal.pone.0108625. eCollection 2014.


Defining the factors that contribute to on-target specificity of antisense oligonucleotides.

Lima WF, Vickers TA, Nichols J, Li C, Crooke ST.

PLoS One. 2014 Jul 29;9(7):e101752. doi: 10.1371/journal.pone.0101752. eCollection 2014.


Phosphorothioate oligonucleotides can displace NEAT1 RNA and form nuclear paraspeckle-like structures.

Shen W, Liang XH, Crooke ST.

Nucleic Acids Res. 2014 Jul;42(13):8648-62. doi: 10.1093/nar/gku579. Epub 2014 Jul 10.


TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co-localize in oligonucleotide-induced nuclear bodies in mammalian cells.

Liang XH, Shen W, Sun H, Prakash TP, Crooke ST.

Nucleic Acids Res. 2014 Jul;42(12):7819-32. doi: 10.1093/nar/gku484. Epub 2014 May 26.


Human RNase H1 is associated with protein P32 and is involved in mitochondrial pre-rRNA processing.

Wu H, Sun H, Liang X, Lima WF, Crooke ST.

PLoS One. 2013 Aug 22;8(8):e71006. doi: 10.1371/journal.pone.0071006. eCollection 2013.


RNA helicase A is not required for RISC activity.

Liang XH, Crooke ST.

Biochim Biophys Acta. 2013 Oct;1829(10):1092-101. doi: 10.1016/j.bbagrm.2013.07.008. Epub 2013 Jul 26.


Lipid nanoparticles improve activity of single-stranded siRNA and gapmer antisense oligonucleotides in animals.

Prakash TP, Lima WF, Murray HM, Elbashir S, Cantley W, Foster D, Jayaraman M, Chappell AE, Manoharan M, Swayze EE, Crooke ST.

ACS Chem Biol. 2013 Jul 19;8(7):1402-6. doi: 10.1021/cb4001316. Epub 2013 May 2.


Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.

Graham MJ, Lee RG, Bell TA 3rd, Fu W, Mullick AE, Alexander VJ, Singleton W, Viney N, Geary R, Su J, Baker BF, Burkey J, Crooke ST, Crooke RM.

Circ Res. 2013 May 24;112(11):1479-90. doi: 10.1161/CIRCRESAHA.111.300367. Epub 2013 Mar 29.


Transfection of siRNAs can alter miRNA levels and trigger non-specific protein degradation in mammalian cells.

Liang XH, Hart CE, Crooke ST.

Biochim Biophys Acta. 2013 May;1829(5):455-68. doi: 10.1016/j.bbagrm.2013.01.011. Epub 2013 Feb 8.


Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B.

Crooke ST, Geary RS.

Br J Clin Pharmacol. 2013 Aug;76(2):269-76. doi: 10.1111/j.1365-2125.2012.04469.x. Review.


Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression.

Yu D, Pendergraff H, Liu J, Kordasiewicz HB, Cleveland DW, Swayze EE, Lima WF, Crooke ST, Prakash TP, Corey DR.

Cell. 2012 Aug 31;150(5):895-908. doi: 10.1016/j.cell.2012.08.002.


Single-stranded siRNAs activate RNAi in animals.

Lima WF, Prakash TP, Murray HM, Kinberger GA, Li W, Chappell AE, Li CS, Murray SF, Gaus H, Seth PP, Swayze EE, Crooke ST.

Cell. 2012 Aug 31;150(5):883-94. doi: 10.1016/j.cell.2012.08.014.


siRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

Vickers TA, Crooke ST.

Nucleic Acids Res. 2012 Jul;40(13):6223-34. doi: 10.1093/nar/gks239. Epub 2012 Mar 15.


U1 adaptors result in reduction of multiple pre-mRNA species principally by sequestering U1snRNP.

Vickers TA, Sabripour M, Crooke ST.

Nucleic Acids Res. 2011 May;39(10):e71. doi: 10.1093/nar/gkr150. Epub 2011 Mar 16.


Depletion of key protein components of the RISC pathway impairs pre-ribosomal RNA processing.

Liang XH, Crooke ST.

Nucleic Acids Res. 2011 Jun;39(11):4875-89. doi: 10.1093/nar/gkr076. Epub 2011 Feb 14.

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