Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Gene regulation: biology of antisense RNA and DNA.
Raven Press Ser Mol Cell Biol; 1:1-364 1992. Unique Identifier : AIDSLINE ICDB/93689043 Anonymous; No affiliation given
Abstract:
Current interest in antisense technology started with studies published in 1984, although endogenous antisense mechanisms had been identified and tested almost two decades before. Antisense transgenes in plants, slime mold, and other nonvertebrate systems yielded nearly complete elimination of target gene expression, but in transgenic mice target gene expression was inhibited only 85-95%. Antisense technology and the basic science behind it are reviewed, including regulation of eukaryotic gene expression by natural antisense transcripts (the modifying reaction) and by naturally occurring antisense RNA; a cellular activity that changes the structure of double-stranded RNA; ribozyme construction, reactivities, and utilities; principles of ribozyme design and use as antisense and therapeutic agents; trans-acting hammerhead ribozymes in vivo; psoralen-derived antisense oligonucleoside methylphosphonates; thermodynamics of antisense oligonucleotide hybridization; control of gene expression by antisense and antigene oligonucleotide-intercalator constructs; antisense DNA therapeutics (neutral analogs and their stereochemistry); pharmaceutical aspects of the biological stability and membrane transport characteristics of antisense oligonucleotides; liposomal delivery as a new approach to transport antisense nucleotides; inhibition of mRNA translation by antisense sequences; use of antisense RNA to study post-transcriptional regulatory processes; chimeric antisense RNAs; antisense inactivation of developmental genes in Dictyostelium; use of ribozymes in plants (plant viral resistance); antisense in Xenopus oocytes and embryos; antisense RNA in mammalian embryos; chemically modified oligodeoxynucleotide analogs regulating viral and cellular gene expression; the potential for antisense inhibition of retroviral replication mediated by retroviral vectors; cellular uptake and anti-HIV activity of oligonucleotides and their analogs; antisense inhibition of gene expression as a tool for studying the role of N-myc in the growth and differentiation of neuroectoderm-derived cells; antisense approaches to assessing oncogene signaling pathways; phosphorothioate oligomers (inhibitors of oncogene expression in tumor cells and tools for gene function analysis); and platelet-derived growth factor, transformation, and antisense (the need for models).
Keywords: Cell Division DNA, Antisense/*PHYSIOLOGY Gene Expression Regulation Neoplasms/PATHOLOGY Oligonucleotides, Antisense RNA, Antisense/*PHYSIOLOGY RNA, Catalytic/METABOLISM Virus Replication MONOGRAPH 930430
M9340827
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