AI Article Synopsis
- Researchers focused on finding accessible target sites within the HIV-1 genome to improve treatment effectiveness using antisense technology.
- Four optimal sites were identified in the structured 5'-UTR region for targeting with 20-mer oligonucleotides.
- Antisense LNA oligonucleotides showed the highest effectiveness in blocking HIV-1 replication and could potentially lead to new antiviral treatments.
Article Abstract
Background: A primary concern when targeting HIV-1 RNA by means of antisense related technologies is the accessibility of the targets. Using a library selection approach to define the most accessible sites for 20-mer oligonucleotides annealing within the highly structured 5'-UTR of the HIV-1 genome we have shown that there are at least four optimal targets available.
Results: The biological effect of antisense DNA and LNA oligonucleotides, DNA- and LNAzymes targeted to the four most accessible sites was tested for their abilities to block reverse transcription and dimerization of the HIV-1 RNA template in vitro, and to suppress HIV-1 production in cell culture. The neutralization of HIV-1 expression declined in the following order: antisense LNA > LNAzymes > DNAzymes and antisense DNA. The LNA modifications strongly enhanced the in vivo inhibitory activity of all the antisense constructs and some of the DNAzymes. Notably, two of the LNA modified antisense oligonucleotides inhibited HIV-1 production in cell culture very efficiently at concentration as low as 4 nM.
Conclusion: LNAs targeted to experimentally selected binding sites can function as very potent inhibitors of HIV-1 expression in cell culture and may potentially be developed as antiviral drug in patients.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866241 | PMC |
| http://dx.doi.org/10.1186/1742-4690-4-29 | DOI Listing |
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