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Updated: Jul 14, 2026
07:18
High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Chimeric RNase H-competent oligonucleotides directed to the HIV-1 Rev response element
Chrissy E Prater1, Anthony D Saleh, Maggie P Wear
1Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Bioorganic & Medicinal Chemistry
|June 15, 2007
Summary
Chimeric oligonucleotides targeting HIV
Area of Science:
- Molecular Biology
- Antiviral Therapeutics
Background:
- The Human Immunodeficiency Virus (HIV) Rev response element (RRE) is crucial for viral replication.
- Targeting RRE RNA is a potential strategy for developing novel antiviral therapies.
Purpose of the Study:
- To design and synthesize chimeric oligonucleotides targeting the RRE RNA.
- To evaluate the binding affinity, stability, and antiviral activity of these novel oligonucleotides.
Main Methods:
- Synthesis of chimeric oligo-2'-O-methylribonucleotides with 2'-deoxyribonucleotide patches and nuclease-resistant linkages.
- Thermal denaturation and electrophoretic mobility shift assays (EMSA) to assess RNA binding.
- RNase H-mediated hydrolysis assays and cell-based assays to determine antiviral efficacy.
Main Results:
- Chimeric oligonucleotides formed stable duplexes with RRE RNA.
- High-affinity and specific binding to RRE stem-loop II RNA was observed (K(D) ≈ 200 nM).
- Oligonucleotides demonstrated nuclease resistance (>24h half-life) and inhibited RRE-mediated gene expression by ~60%.
Conclusions:
- Novel chimeric oligonucleotides exhibit potent antiviral properties against HIV by targeting RRE RNA.
- These compounds show promise as a new class of antiviral agents.
- Further development could lead to effective HIV therapeutics.
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