Affordable Access

Long-term treatment of human immunodeficiency virus-infected cells with antisense oligonucleotide phosphorothioates.

Authors
  • Lisziewicz, J
  • Sun, D
  • Metelev, V
  • Zamecnik, P
  • Gallo, R C
  • Agrawal, S
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
May 01, 1993
Volume
90
Issue
9
Pages
3860–3864
Identifiers
PMID: 8483903
Source
Medline
License
Unknown

Abstract

The antiviral activity of antisense oligodeoxynucleotide phosphorothioates complementary to the tat gene, the gag mRNA, and the rev mRNA were studied in a long-term infection model. Three antisense oligonucleotides directed to the splice-acceptor site of the tat gene failed to suppress human immunodeficiency virus type 1 replication at 1 microM concentration in long-term culture. In contrast, two oligodeoxynucleotide phosphorothioates (28-mer) complementary to the gag and the rev mRNAs inhibited viral replication for > 80 days, and the antiviral activity was sequence- and length-dependent. In addition, after pretreatment of cells we could reduce the concentration of the antisense oligodeoxynucleotides by > 10-fold and still maintain the inhibition of viral replication. These results suggest that chemotherapy for human immunodeficiency virus type 1 infection with antisense oligodeoxynucleotide phosphorothioates may be achieved by an initial high-dose treatment followed by a lower maintenance dose.

Report this publication

Statistics

Seen <100 times