ArticleProceedings of the National Academy of Sciences of the United States of America2007
Hairpin extensions enhance the efficacy of mycolyl transferase-specific antisense oligonucleotides targeting Mycobacterium tuberculosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- Promising strategies employing nucleic acids as antimicrobial drugs.Molecular therapy. Nucleic acids · 2024Review
- Review
- A New Antisense Phosphoryl Guanidine Oligo-2'-O-Methylribonucleotide Penetrates Into Intracellular Mycobacteria and Suppresses Target Gene Expression.Frontiers in pharmacology · 2019Article
- Advances in therapeutic bacterial antisense biotechnology.Applied microbiology and biotechnology · 2018Review
- Mycobacterial trehalose dimycolate reprograms macrophage global gene expression and activates matrix metalloproteinases.Infection and immunity · 2013Article
- Exposure to a cutinase-like serine esterase triggers rapid lysis of multiple mycobacterial species.The Journal of biological chemistry · 2013Article
- Design, synthesis, and X-ray analysis of a glycoconjugate bound to Mycobacterium tuberculosis antigen 85C.Bioconjugate chemistry · 2012Article
- Bacterial resistance to antisense peptide phosphorodiamidate morpholino oligomers.Antimicrobial agents and chemotherapy · 2012Article
- Internalization of Locked Nucleic Acids/DNA Hybrid Oligomers into Escherichia coli.BioResearch open access · 2012Article
- Targeting the mycobacterial envelope for tuberculosis drug development.Expert review of anti-infective therapy · 2012Review
- Inhibition of aac(6')-Ib-mediated amikacin resistance by nuclease-resistant external guide sequences in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Concurrent growth rate and transcript analyses reveal essential gene stringency in Escherichia coli.PloS one · 2009Article
- Hitting bacteria at the heart of the central dogma: sequence-specific inhibition.Microbial cell factories · 2007Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
We have investigated the efficacy of modifying gene-specific antisense phosphorothioate oligodeoxyribonucleotides (PS-ODNs) by the addition of 5' and 3' hairpin extensions. As a model system, we have targeted the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase protein complex genes encoding three highly related enzymes (antigens 85 A, B, and C). Whereas the addition of a hairpin extension at only one end of the PS-ODNs did not improve their inhibitory capacity, the addition of hairpin extensions at both ends enhanced their capacity to inhibit M. tuberculosis multiplication in comparison with unmodified PS-ODNs. A combination of three 5'-, 3'-hairpin-modified PS-ODNs (HPS-ODNs) targeting each of the three mycolyl transferase transcripts inhibited bacterial growth in broth culture by approximately 1.75 log units (P < 0.0001) and in human THP-1 macrophages by approximately 0.4 log units (P < 0.0001), which to our knowledge has not previously been demonstrated for any PS-ODN; reduced target gene transcription by > or =90%; caused approximately 90% reduction in mycolyl transferase expression; and increased bacterial sensitivity to isoniazid by 8-fold. The growth-inhibitory effect of the HPS-ODNs was gene-specific. Mismatched HPS-ODNs had no growth-inhibitory capacity. This study demonstrates that 5'- and 3'-HPS-ODNs are highly efficacious against M. tuberculosis and supports the further development of antisense technology as a therapeutic modality against tuberculosis.
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