Synthesis, biophysical properties and biological activity of second generation antisense oligonucleotides containing chiral phosphorothioate linkages

Autor: Guillermo Vasquez, Heather M. Murray, Walt F. Lima, Andres Berdeja, Eric E. Swayze, W. Brad Wan, Hans Gaus, Josh G. Nichols, Punit P. Seth, Christopher E. Hart, Michael T. Migawa, Sam Lee

Publikováno v: Nucleic Acids Research

Bicyclic oxazaphospholidine monomers were used to prepare a series of phosphorothioate (PS)-modified gapmer antisense oligonucleotides (ASOs) with control of the chirality of each of the PS linkages within the 10-base gap. The stereoselectivity was d

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b998d608d82c2dde1115aee2213c2418
https://doi.org/10.1093/nar/gku1115

Human Dicer Binds Short Single-strand and Double-strand RNA with High Affinity and Interacts with Different Regions of the Nucleic Acids

Autor: Hans Gaus, Hong Sun, Walt F. Lima, Heather M. Murray, Andres Berdeja, Stanley T. Crooke, Thazha P. Prakash, Josh G. Nichols, Hongjiang Wu

Publikováno v: Journal of Biological Chemistry. 284:2535-2548

Human Dicer is an integral component of the RNA interference pathway. Dicer processes premicro-RNA and double-strand RNA to, respectively, mature micro-RNA and short interfering RNA (siRNA) and transfers the processed products to the RNA-induced sile

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::120ba969bcabbbe9e635ce4beb466708
https://doi.org/10.1074/jbc.m803748200

Allele-Selective Inhibition of Mutant Huntingtin with 2-Thio- and C5- Triazolylphenyl-Deoxythymidine-Modified Antisense Oligonucleotides

Autor: Andrew T. Watt, Michael E. Østergaard, Pawan Kumar, Pawan K. Sharma, Punit P. Seth, Josh G. Nichols, Poul Nielsen

Publikováno v: Østergaard, M E, Kumar, P, Nichols, J, Watt, A, Sharma, P K, Nielsen, P & Seth, P P 2015, ' Allele-Selective Inhibition of Mutant Huntingtin with 2-Thio-and C5-Triazolylphenyl-Deoxythymidine-Modified Antisense Oligonucleotides ', Nucleic Acid Therapeutics, vol. 25, no. 5, pp. 266-274 . https://doi.org/10.1089/nat.2015.0547

We report the effect of introducing a single incorporation of 2-thio-deoxythymidine (2S-dT) or C5-Triazolylphenyl-deoxythymidine (5-TrPh-dT) at four positions within the gap region of RNase H gapmer antisense oligonucleotides (ASOs) for reducing wild

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b13b9c3fad6a832bc3a891027d83f039
https://pubmed.ncbi.nlm.nih.gov/26222265

Structural Requirements at the Catalytic Site of the Heteroduplex Substrate for Human RNase H1 Catalysis

Autor: Balkrishen Bhat, Josh G. Nichols, Walt F. Lima, Stanley T. Crooke, Mike T. Migawa, Hongjiang Wu, Thazha P. Prakash, Tadensz K. Wyrzykiewicz

Publikováno v: Journal of Biological Chemistry. 279:36317-36326

Human RNase H1 cleaves RNA exclusively in an RNA/DNA duplex; neither double-strand DNA nor double-strand RNA is a viable substrate. Previous studies suggest that the helical geometry and sugar conformation of the DNA and RNA may play a role in the se

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d88b5bc3df219a40c6fdba057ed3ecf0
https://doi.org/10.1074/jbc.m405035200

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

Autor: Josh G. Nichols, Stanley T. Crooke, Timothy A. Vickers, Cheryl S. Li, Walt F. Lima

Publikováno v: PLoS ONE
PLoS ONE, Vol 9, Iss 7, p e101752 (2014)

To better understand the factors that influence the activity and specificity of antisense oligonucleotides (ASOs), we designed a minigene encoding superoxide dismutase 1 (SOD-1) and cloned the minigene into vectors for T7 transcription of pre-mRNA an

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::292ad3b6e7c1546da6065ca85380eff5
https://pubmed.ncbi.nlm.nih.gov/25072142