Capillary gel electrophoresis and antisense therapeutics. Analysis of DNA analogs.
Capillary gel electrophoresis (CGE) has become an effective tool for the analysis of antisense oligonucleotides. As these compounds begin to show promise in the pharmaceutical field, CGE is often used to determine the quality of chemically synthesized DNA analogs, which are presently being studied as potential antisense therapeutics. The demand for gel capillaries to process high resolving power and provide statistically meaningful data has indirectly provided a better understanding of what is required to denature single-stranded oligonucleotides. For CGE to be useful for the analysis of oligonucleotides in general, an internal standard is often employed; however, apart from being a strictly quantitative tool, CGE has the capability to be useful in a wide range of applications within the field of antisense therapeutics. CGE can be used in conjunction with HPLC to determine an effective method for the purification of crude oligonucleotide solutions. It has also proven useful in determining whether or not a DNA analog can promote the ribonuclease H-mediated hydrolysis of RNA. An understanding of the interactions between antisense oligonucleotides and nucleases in general is critical for determining how antisense oligonucleotides function within a biological system.
DeDionisio
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Lynx Therapeutics Incorporated, Hayward, CA 94545, USA.
Lloyd
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D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis*; D019075:Electrophoresis, Capillary / Q000379:methods / Q000706:statistics & numerical data; D004722:Endoribonucleases / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000032:analysis* / Q000627:therapeutic use; D012313:RNA / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D012313:RNA; D004247:DNA; D004722:Endoribonucleases