ArticleRNA (New York, N.Y.)2010
Titers of lentiviral vectors encoding shRNAs and miRNAs are reduced by different mechanisms that require distinct repair strategies.
Article in RNA (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
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- Evaluation of the Elements of Short Hairpin RNAs in Developing shRNA-Containing CAR T Cells.Cancers · 2023Article
- MicroRNAs in Metastasis and the Tumour Microenvironment.International journal of molecular sciences · 2021Review
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- Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy.Molecular therapy. Methods & clinical development · 2020Article
- MicroRNAs and Metastasis.Cancers · 2019Review
- Superior lentiviral vectors designed for BSL-0 environment abolish vector mobilization.Gene therapy · 2018Article
- DROSHA Knockout Leads to Enhancement of Viral Titers for Vectors Encoding miRNA-Adapted shRNAs.Molecular therapy. Nucleic acids · 2018Article
- RNA virus building blocks-miRNAs not included.PLoS pathogens · 2018Article
- Association of MicroRNA Biogenesis Genes Polymorphisms with Ischemic Stroke Susceptibility and Post-Stroke Mortality.Journal of stroke · 2018Article
- Type III Transforming Growth Factor-Stem cells international · 2018Article
- A lentiviral vector bearing a reverse intron demonstrates superior expression of both proteins and microRNAs.RNA biology · 2017Article
- Improving miRNA Delivery by Optimizing miRNA Expression Cassettes in Diverse Virus Vectors.Human gene therapy methods · 2017Review
- Silencing of HIV-1 by AgoshRNA molecules.Gene therapy · 2017Article
- Review
- RNA therapeutics - The potential treatment for myocardial infarction.Regenerative therapy · 2016Review
- Prospects for Foamy Viral Vector Anti-HIV Gene Therapy.Biomedicines · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNAi-based gene therapy is a powerful approach to treat viral infections because of its high efficiency and sequence specificity. The HIV-1-based lentiviral vector system is suitable for the delivery of RNAi inducers to HIV-1 susceptible cells due to its ability to transduce nondividing cells, including hematopoietic stem cells, and its ability for stable transgene delivery into the host cell genome. However, the presence of anti-HIV short hairpin RNA (shRNA) and microRNA (miRNA) cassettes can negatively affect the lentiviral vector titers. We show that shRNAs, which target the vector genomic RNA, strongly reduced lentiviral vector titers but inhibition of the RNAi pathway via saturation could rescue vector production. The presence of miRNAs in the vector RNA genome (sense orientation) results in a minor titer reduction due to Drosha processing. A major cause for titer reduction of miRNA vectors is due to incompatibility of the cytomegalovirus promoter with the lentiviral vector system. Replacement of this promoter with an inducible promoter resulted in an almost complete restoration of the vector titer. We also showed that antisense poly(A) signal sequences can have a dramatic effect on the vector titer. These results show that not all sequences are compatible with the lentiviral vector system and that care should be taken in the design of lentiviral vectors encoding RNAi inducers.
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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.