title: Two problems in antisense biotechnology: in vitro delivery and the design of antisense experiments.
abstract: Antisense oligonucleotides are invaluable reagents for the specific downregulation of gene expression. In the absence of a carrier, charged oligonucleotides (e.g., phosphorothioates) can interact with a large number of cell surface proteins, but tend to be internalized into the endosomal/lysosomal compartment. However, they can be successfully delivered to the nuclei of diverse cell types via the use of a wide variety of reagents, including cationic lipids, and cationic polyamines. Over the past several years, a more general understanding of the rules governing the interpretation of data derived from antisense experiments has been reached. These are discussed with emphasis on how to avoid some of the confounding features of this important, emerging technology.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA. stein@cuccfa.ccc.columbia.edu
authors.forename: C A
authors.initials: CA
authors.lastname: Stein
mesh_terms: D000818:Animals; D001709:Biotechnology / Q000379:methods*; D002451:Cell Compartmentation; D004337:Drug Carriers / Q000378:metabolism; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism* / Q000494:pharmacology; D012107:Research Design; D013873:Thionucleotides / Q000378:metabolism / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides