ArticleNucleic acids research2006
Engineered external guide sequences are highly effective in inducing RNase P for inhibition of gene expression and replication of human cytomegalovirus.
Article in Nucleic acids research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- External Guide Sequence Effectively Suppresses the Gene Expression and Replication of Herpes Simplex Virus 2.Molecules (Basel, Switzerland) · 2024Article
- Inhibition of human cytomegalovirus major capsid protein expression and replication by ribonuclease P-associated external guide sequences.RNA (New York, N.Y.) · 2019Article
- Inhibition of Murine Cytomegalovirus Infection in Animals by RNase P-Associated External Guide Sequences.Molecular therapy. Nucleic acids · 2017Article
- RNase P Ribozymes Inhibit the Replication of Human Cytomegalovirus by Targeting Essential Viral Capsid Proteins.Viruses · 2015Article
- Engineered RNase P ribozymes effectively inhibit human cytomegalovirus gene expression and replication.Viruses · 2014Article
- Cytomegalovirus antivirals and development of improved animal models.Expert opinion on drug metabolism & toxicology · 2011Review
- Effective inhibition of HCMV UL49 gene expression and viral replication by oligonucleotide external guide sequences and RNase P.Virology journal · 2010Article
- Generation of an external guide sequence library for a reverse genetic screen in Caenorhabditis elegans.BMC biotechnology · 2009Article
- Gene silencing in the therapy of influenza and other respiratory diseases: Targeting to RNase P by use of External Guide Sequences (EGS).Biologics : targets & therapy · 2007Article
- Progress and prospects: RNA-based therapies for treatment of HIV infection.Gene therapy · 2007Review
- Inhibition of gene expression in human cells using RNase P-derived ribozymes and external guide sequences.Biochimica et biophysica actaReview
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
External guide sequences (EGSs), which are RNA molecules derived from natural tRNAs, bind to a target mRNA and render the mRNA susceptible to hydrolysis by RNase P, a tRNA processing enzyme. Using an in vitro selection procedure, we have previously generated EGS variants that efficiently direct human RNase P to cleave a target mRNA in vitro. In this study, a variant was used to target the overlapping region of the mRNAs encoding human cytomegalovirus (HCMV) essential transcription regulatory factors IE1 and IE2. The EGS variant was approximately 25-fold more active in inducing human RNase P to cleave the mRNA in vitro than the EGS derived from a natural tRNA. Moreover, a reduction of 93% in IE1/IE2 gene expression and a reduction of 3000-fold in viral growth were observed in HCMV-infected cells that expressed the variant, while cells expressing the tRNA-derived EGS exhibited a reduction of 80% in IE1/IE2 expression and an inhibition of 150-fold in viral growth. Our results provide the first direct evidence that EGS variant is highly effective in blocking HCMV gene expression and growth and furthermore, demonstrate the feasibility of developing effective EGS RNA variants for anti-HCMV applications by using in vitro selection procedures.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.