Inhibition of Human Immunodeficiency Virus Replication by Antisense Oligodeoxynucleotides

Twenty different target sites within human immunodeficiency virus (HIV) RNA were selected for studies of inhibition of HIV replication by antisense oligonucleotides. Target sites were selected based on their potential capacity to block recognition functions during viral replication. Antisense oligom...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1988-08, Vol.85 (15), p.5507-5511
Main Authors: Goodchild, John, Agrawal, Sudhir, Civeira, Maria P., Sarin, Prem S., Sun, Daisy, Zamecnik, Paul C.
Format: Article
Language:English
Subjects:
AIDS
AIDS related complex
Animals
Antiviral Agents - pharmacology
Antiviral Agents - toxicity
Base Sequence
Dosage
Female
HIV
HIV - drug effects
HIV - physiology
human immunodeficiency virus
Humans
Male
Mice
Molecular Sequence Data
Nucleic Acid Hybridization
Oligomers
Oligonucleotides
Oligonucleotides - pharmacology
Oligonucleotides - toxicity
Oligonucleotides, Antisense
Protein Biosynthesis
Retroviridae
RNA
RNA Splicing
RNA, Viral - genetics
Syncytia
Transcription, Genetic
Virus Replication - drug effects
Viruses
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Summary:Twenty different target sites within human immunodeficiency virus (HIV) RNA were selected for studies of inhibition of HIV replication by antisense oligonucleotides. Target sites were selected based on their potential capacity to block recognition functions during viral replication. Antisense oligomers complementary to sites within or near the sequence repeated at the ends of retrovirus RNA (R region) and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting virus replication was also investigated, and preliminary toxicity studies in mice show that these compounds are toxic only at high levels. The results indicate potential usefulness for these oligomers in the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex either alone or in combination with other drugs.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.85.15.5507