ArticleProceedings of the National Academy of Sciences of the United States of America2006
Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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126 citing papers in PubMed, 244 citations in OpenAlex.
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- Lentiviral Vectors: From Wild-Type Viruses to Efficient Multi-Functional Delivery Vectors.International journal of molecular sciences · 2025Review
- The Era of Gene Therapy: The Advancement of Lentiviral Vectors and Their Pseudotyping.Viruses · 2025Review
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- Development and validation of optimized lentivirus-like particles for gene editing tool delivery with Gag-Only strategy.European journal of medical research · 2025Article
- Molecular Engineering of Virus Tropism.International journal of molecular sciences · 2024Review
- PTEN Mediates the Silencing of Unintegrated HIV-1 DNA.Viruses · 2024Article
- HIV Preintegration Transcription and Host Antagonism.Current HIV research · 2023Article
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- Maybe you can turn me on: CRISPRa-based strategies for therapeutic applications.Cellular and molecular life sciences : CMLS · 2022Review
- Cancer gene therapy goes viral: viral vector platforms come of age.Radiology and oncology · 2022Article
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- Gene Therapy: The Next-Generation Therapeutics and Their Delivery Approaches for Neurological Disorders.Frontiers in genome editing · 2022Review
- Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses.Clinical ophthalmology (Auckland, N.Z.) · 2022Review
- Hematopoietic stem and progenitors cells gene editing: Beyond blood disorders.Frontiers in genome editing · 2022Review
- Improved Functionality of Integration-Deficient Lentiviral Vectors (IDLVs) by the Inclusion of ISPharmaceutics · 2021Article
66 more citing papers are in PubMed but not listed here.
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8 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Lentivirus-derived vectors are among the most promising viral vectors for gene therapy currently available, but their use in clinical practice is limited by the associated risk of insertional mutagenesis. We have overcome this problem by developing a nonintegrative lentiviral vector derived from HIV type 1 with a class 1 integrase (IN) mutation (replacement of the 262RRK motif by AAH). We generated and characterized HIV type 1 vectors carrying this deficient enzyme and expressing the GFP or neomycin phosphotransferase transgene (NEO) under control of the immediate early promoter of human CMV. These mutant vectors efficiently transduced dividing cell lines and nondividing neural primary cultures in vitro. After transduction, transient GFP fluorescence was observed in dividing cells, whereas long-term GFP fluorescence was observed in nondividing cells, consistent with the viral genome remaining episomal. Moreover, G418 selection of cells transduced with vectors expressing the NEO gene showed that residual integration activity was lower than that of the intact IN by a factor of 500-1,250. These nonintegrative vectors were also efficient in vivo, allowing GFP expression in mouse brain cells after the stereotactic injection of IN-deficient vector particles. Thus, we have developed a generation of lentiviral vectors with a nonintegrative phenotype of great potential value for secure viral gene transfer in clinical applications.
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