Antisense inhibition of oncogene expression.
To understand the role of individual genes in regulating biological processes, one must be able to interfere specifically with either their expression or function. While monoclonal antibodies have proven very useful in studying cell surface proteins, the specific inhibition of intracellular proteins in viable cells is a much more difficult problem. The goal of antisense technology is to develop small oligonucleotides, plasmids, or retroviral vectors which can be readily introduced into living cells in order to inhibit specific gene expression. In this review, we briefly describe the principles of antisense usage, including problems of cellular uptake and intracellular distribution, mechanism of antisense action, and the properties of various oligonucleotide derivatives. In addition we present several examples of the biological effects of antisense administration used to study the role of specific genes in the regulation of cell growth and differentiation.
Neckers
L
L
Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Whitesell
L
L
Rosolen
A
A
Geselowitz
D A
DA
D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology; D016373:DNA, Antisense / Q000737:chemistry / Q000494:pharmacology; D066246:ErbB Receptors / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000502:physiology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology; D009857:Oncogenes / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D016372:RNA, Antisense / Q000737:chemistry / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology; D018168:Receptors, Retinoic Acid; D016914:Ribonuclease H / Q000502:physiology
D016375:Antisense Elements (Genetics); D002352:Carrier Proteins; D016373:DNA, Antisense; D006133:Growth Substances; D007378:Interleukins; D016376:Oligonucleotides, Antisense; D015513:Oncogene Proteins; D016372:RNA, Antisense; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; C027928:retinol binding protein receptor; D011494:Protein Kinases; D066246:ErbB Receptors; D016914:Ribonuclease H