Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Antisense strategies and therapeutic applications.
Am J Health Syst Pharm. 1996 Jan 15;53(2):151-60; quiz 182-3. Unique Identifier : AIDSLINE MED/96263414 Putnam DA; Department of Pharmaceutics and Pharmaceutical Chemistry,; University of Utah, Salt Lake City, UT 84112, USA.
Abstract:
The concepts underlying the antisense approach to disease therapy are discussed, and potential applications are examined. Antisense therapeutic agents bind to DNA or RNA sequences, blocking the synthesis of cellular proteins with unparalleled specificity. Transcription and translation are the two processes with which the agents interfere. There are three major classes of antisense agents: antisense sequences, commonly called antisense oligonucleotides; antigene sequences; and ribozymes. Antisense sequences are derivatives of nucleic acids that hybridize cytosolic messenger RNA (mRNA) sense strands through hydrogen bonding to complementary nucleic acid bases. Antigene sequences hybridize double-stranded DNA in the nucleus, forming triple helixes. Ribozymes, rather than inhibiting protein synthesis simply by binding to a single targeted mRNA, combine enzymatic processes with the specificity of antisense base pairing, creating a molecule that can incapacitate multiple targeted mRNAs. Antisense therapeutic agents are being investigated in vitro and in vivo for use in treating human immunodeficiency virus infection, hepatitis B virus infection, herpes simplex virus infection, papillomavirus infection, cancer, restenosis, rheumatoid arthritis, and allergic disorders. Although many results are preliminary, some are promising and have led to clinical trials. A major goal in developing methods of delivering antisense agents is to reduce their susceptibility to nucleases while retaining their ability to bind to targeted sites. Modification of the phosphodiester linkages in oligonucleotides can lend the sequences enzymatic stability without affecting their binding capacities. Carrier systems designed to protect the antisense structure and improve passage through the cell membrane include liposomes, water-soluble polymers, and nanoparticles. The pharmacokinetics of antisense agents are under investigation. Antisense therapeutic agents have the potential to become an integral part of medicinal regimens.
Keywords: Antisense Elements (Genetics)/ADMINISTRATION & DOSAGE/METABOLISM/ *THERAPEUTIC USE Drug Carriers Hepatitis B Virus/DRUG EFFECTS Herpesvirus 1, Human/DRUG EFFECTS Herpesvirus 4, Human/DRUG EFFECTS HIV Infections/DRUG THERAPY Neoplasms/DRUG THERAPY Oligonucleotides, Antisense/CHEMISTRY/METABOLISM/PHARMACOKINETICS Papillomavirus/DRUG EFFECTS RNA, Catalytic/CHEMISTRY/CLASSIFICATION/GENETICS/METABOLISM Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL 961030
M96A1391
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
