Walt F Lima

Summary

Affiliation: Isis Pharmaceuticals
Country: USA

Publications

  1. ncbi request reprint Binding affinity and specificity of Escherichia coli RNase H1: impact on the kinetics of catalysis of antisense oligonucleotide-RNA hybrids
    W F Lima
    Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    Biochemistry 36:390-8. 1997
  2. ncbi request reprint The positional influence of the helical geometry of the heteroduplex substrate on human RNase H1 catalysis
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California, USA
    Mol Pharmacol 71:73-82. 2007
  3. ncbi request reprint Structural requirements at the catalytic site of the heteroduplex substrate for human RNase H1 catalysis
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
    J Biol Chem 279:36317-26. 2004
  4. doi request reprint Human Dicer binds short single-strand and double-strand RNA with high affinity and interacts with different regions of the nucleic acids
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California 92008, USA
    J Biol Chem 284:2535-48. 2009
  5. ncbi request reprint Human RNase H1 uses one tryptophan and two lysines to position the enzyme at the 3'-DNA/5'-RNA terminus of the heteroduplex substrate
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California 92008, USA
    J Biol Chem 278:49860-7. 2003
  6. ncbi request reprint Human RNase H1 activity is regulated by a unique redox switch formed between adjacent cysteines
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California 92008, USA
    J Biol Chem 278:14906-12. 2003
  7. pmc Binding and cleavage specificities of human Argonaute2
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    J Biol Chem 284:26017-28. 2009
  8. ncbi request reprint Human RNase H1 discriminates between subtle variations in the structure of the heteroduplex substrate
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California, USA
    Mol Pharmacol 71:83-91. 2007
  9. ncbi request reprint Cleavage of single strand RNA adjacent to RNA-DNA duplex regions by Escherichia coli RNase H1
    W F Lima
    Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    J Biol Chem 272:27513-6. 1997
  10. pmc Highly efficient endonucleolytic cleavage of RNA by a Cys(2)His(2) zinc-finger peptide
    W F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
    Proc Natl Acad Sci U S A 96:10010-5. 1999

Detail Information

Publications24

  1. ncbi request reprint Binding affinity and specificity of Escherichia coli RNase H1: impact on the kinetics of catalysis of antisense oligonucleotide-RNA hybrids
    W F Lima
    Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    Biochemistry 36:390-8. 1997
    ..These results offer further insights into the physical binding properties of the RNase H-substrate interaction as well as the design of effective antisense oligonucleotides...
  2. ncbi request reprint The positional influence of the helical geometry of the heteroduplex substrate on human RNase H1 catalysis
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California, USA
    Mol Pharmacol 71:73-82. 2007
    ..Finally, these results provide a method for enhancing the human RNase H1 activity of chimeric antisense oligonucleotides (ASO) as well as the design of more potent ASO drugs...
  3. ncbi request reprint Structural requirements at the catalytic site of the heteroduplex substrate for human RNase H1 catalysis
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
    J Biol Chem 279:36317-26. 2004
    ....
  4. doi request reprint Human Dicer binds short single-strand and double-strand RNA with high affinity and interacts with different regions of the nucleic acids
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California 92008, USA
    J Biol Chem 284:2535-48. 2009
    ..These data suggest that the siRNAs and ssRNAs interact predominantly with the PAZ domain of the enzyme. Finally, the tightest binding siRNAs were also more potent inhibitors of gene expression...
  5. ncbi request reprint Human RNase H1 uses one tryptophan and two lysines to position the enzyme at the 3'-DNA/5'-RNA terminus of the heteroduplex substrate
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California 92008, USA
    J Biol Chem 278:49860-7. 2003
    ..These results offer further insights into the interaction between human RNase H1 and the heteroduplex substrate as well as approaches to enhance the design of effective antisense oligonucleotides...
  6. ncbi request reprint Human RNase H1 activity is regulated by a unique redox switch formed between adjacent cysteines
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California 92008, USA
    J Biol Chem 278:14906-12. 2003
    ....
  7. pmc Binding and cleavage specificities of human Argonaute2
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    J Biol Chem 284:26017-28. 2009
    ....
  8. ncbi request reprint Human RNase H1 discriminates between subtle variations in the structure of the heteroduplex substrate
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California, USA
    Mol Pharmacol 71:83-91. 2007
    ..The data presented here offer further insights into the role substrate structure plays in directing human RNase H1 activity as well as the design of effective ASOs...
  9. ncbi request reprint Cleavage of single strand RNA adjacent to RNA-DNA duplex regions by Escherichia coli RNase H1
    W F Lima
    Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    J Biol Chem 272:27513-6. 1997
    ..These results offer additional insights into the binding directionality of RNase H with respect to the heteroduplex substrate...
  10. pmc Highly efficient endonucleolytic cleavage of RNA by a Cys(2)His(2) zinc-finger peptide
    W F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
    Proc Natl Acad Sci U S A 96:10010-5. 1999
    ..These observations raise interesting questions about the potential biological roles of zinc-finger proteins...
  11. ncbi request reprint Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs
    Hongjiang Wu
    Department of Core Technology, Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    J Biol Chem 279:17181-9. 2004
    ..Further, we show that there are several additional previously undescribed RNases H in human cells that may participate in the effects of DNA-like antisense oligonucleotides...
  12. pmc Off-target and a portion of target-specific siRNA mediated mRNA degradation is Ago2 'Slicer' independent and can be mediated by Ago1
    Timothy A Vickers
    Antisense Core Research, Isis Pharmaceuticals, Carlsbad, CA 92008, USA
    Nucleic Acids Res 37:6927-41. 2009
    ..Finally, we present data suggesting that a significant portion of on-target siRNA activity is also Ago2 cleavage independent, however, this activity does not appear to be P-body associated...
  13. pmc Reduced levels of Ago2 expression result in increased siRNA competition in mammalian cells
    Timothy A Vickers
    Isis Pharmaceuticals 1896 Rutherford Road, Carlsbad, CA 92008, USA
    Nucleic Acids Res 35:6598-610. 2007
    ..RISC reloading and subsequent induction of detectable cleavage of a new target RNA, requires about 9-12 h following the initial transfection...
  14. doi request reprint Single-stranded siRNAs activate RNAi in animals
    Walt F Lima
    Core Antisense Research, Isis Pharmaceuticals Inc, Carlsbad, CA 92010, USA
    Cell 150:883-94. 2012
    ..Identification of potent ss-siRNAs offers an additional option for RNAi therapeutics and an alternate perspective on RNAi mechanism...
  15. ncbi request reprint Antisense phosphorothioate oligodeoxyribonucleotide targeted against ICAM-1: synthetic and biological characterization of a process-related impurity formed during oligonucleotide synthesis
    Vasulinga T Ravikumar
    Isis Pharmaceuticals, Inc, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
    Bioorg Med Chem 11:4673-9. 2003
    ..Biological properties of the compound have been determined. Based on these data, it can be concluded that this species (3'-TPT) has biological properties similar to parent drug...
  16. ncbi request reprint The influence of antisense oligonucleotide-induced RNA structure on Escherichia coli RNase H1 activity
    W F Lima
    Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    J Biol Chem 272:18191-9. 1997
    ..These results offer further insights into the role of antisense-induced RNA structure on RNase H activity and may facilitate the design of effective antisense oligonucleotides...
  17. pmc ss-siRNAs allele selectively inhibit ataxin-3 expression: multiple mechanisms for an alternative gene silencing strategy
    Jing Liu
    Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA and Department of Medicinal Chemistry and Core Antisense Research, Isis Pharmaceuticals, Carlsbad, CA 92010, USA
    Nucleic Acids Res 41:9570-83. 2013
    ....
  18. pmc Human RNase H1 is associated with protein P32 and is involved in mitochondrial pre-rRNA processing
    Hongjiang Wu
    Department of Core Antisense Research, Isis Pharmaceuticals, Inc, Carlsbad, California, United States of America
    PLoS ONE 8:e71006. 2013
    ..Further, the results identify P32 as a member of the 'RNase H1 degradosome' and the key P32 enhances the enzymatic efficiency of human RNase H1...
  19. ncbi request reprint Biologically active antisense phosphorothioate oligodeoxyribonucleotides: synthesis, characterization, and studies of 3'-terminal phosphorothioate monoester analogues
    Vasulinga T Ravikumar
    Isis Pharmaceuticals, Carlsbad, California 92008, USA
    Nucleosides Nucleotides Nucleic Acids 23:149-60. 2004
    ..Influence of the added negative charge on activation of duplexes by RNase H was investigated. No additional help in recruitment of RNase H was observed...
  20. ncbi request reprint Antisense oligonucleotides: efficient synthesis of 2'-O-methoxyethyl phosphorothioate oligonucleotides using 4,5-dicyanoimidazole. Are these oligonucleotides comparable to those synthesized using 1H-tetrazole as coupling activator?
    Zhiwei Wang
    Isis Pharmaceuticals, Inc, 2282 Faraday Avenue, Carlsbad, CA 92008, USA
    Bioorg Med Chem 14:5049-60. 2006
    ..This extensive study will help the oligonucleotide therapeutic industry to move from using a potentially explosive activator (1H-tetrazole) to a safe activator (DCI)...
  21. ncbi request reprint Investigating the structure of human RNase H1 by site-directed mutagenesis
    H Wu
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, Carlsbad, California 92008, USA
    J Biol Chem 276:23547-53. 2001
    ....
  22. ncbi request reprint Properties of cloned and expressed human RNase H1
    H Wu
    Isis Pharmaceuticals, Inc, Carlsbad, California 92082, USA
    J Biol Chem 274:28270-8. 1999
    ..The minimum RNA-DNA duplex length that supports cleavage is 6 base pairs, and the minimum RNA-DNA "gap size" that supports cleavage is 5 base pairs...
  23. ncbi request reprint Control of complexity constraints on combinatorial screening for preferred oligonucleotide hybridization sites on structured RNA
    T W Bruice
    Department of Research Medicinal Chemistry, Isis Pharmaceuticals, Carlsbad, California 92008, USA
    Biochemistry 36:5004-19. 1997
    ....
  24. ncbi request reprint Molecular cloning and expression of cDNA for human RNase H
    H Wu
    Department of Molecular Pharmacology, Isis Pharmaceuticals, Carlsbad, CA 92008, USA
    Antisense Nucleic Acid Drug Dev 8:53-61. 1998
    ..6% amino acid identity) and to other RNase H enzymes homologous to E. coli RNase HI. The enzyme is encoded by a single gene that is at least 10 kb in length and is expressed ubiquitously in human cells and tissues...