ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
A TLR and non-TLR mediated innate response to lentiviruses restricts hepatocyte entry and can be ameliorated by pharmacological blockade.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. 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, 45 citations in OpenAlex.
- Reprogramming innate immunity through viral interference: A double-edged strategy for enhancing and containing gene therapies.Molecular therapy. Nucleic acids · 2026Review
- Metabolic Dysfunction-Associated Steatotic Liver Disease and Emerging Oligonucleotide Therapies.International journal of biological sciences · 2026Review
- How Close Are We to Achieving Durable and Efficacious Gene Therapy for Hemophilia A and B?Genes · 2025Review
- Inhibition of IFNAR-JAK signaling enhances tolerability and transgene expression of systemic non-viral DNA delivery.Molecular therapy. Nucleic acids · 2025Article
- Enhancing the potency of in vivo lentiviral vector mediated gene therapy to hepatocytes.Nature communications · 2025Article
- Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.Cell communication and signaling : CCS · 2025Review
- Viral-mediated gene therapy in pediatric neurological disorders.World journal of pediatrics : WJP · 2024Review
- TLR9-independent CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The RLR intrinsic antiviral system is expressed in neural retina and restricts lentiviral transduction of human Mueller cells.Experimental eye research · 2023Article
- Innate Immune Response to Viral Vectors in Gene Therapy.Viruses · 2023Review
- DC-targeting lentivectors for cancer immunotherapy.Immunotherapy advances · 2023Review
- Amelioration of experimental tendinopathy by lentiviral CD44 gene therapy targeting senescence-associated secretory phenotypes.Molecular therapy. Methods & clinical development · 2022Article
- Antiviral immunity and nucleic acid sensing in haematopoietic stem cell gene engineering.Gene therapy · 2021Review
- Enhancing therapeutic efficacy of in vivo platelet-targeted gene therapy in hemophilia A mice.Blood advances · 2020Article
- Dosing and Re-Administration of Lentiviral Vector forMolecular therapy. Methods & clinical development · 2020Article
- Immune Responses to Viral Gene Therapy Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies for Hemophilia A Patients.International journal of molecular and cellular medicine · 2020Review
- Modulation of immune responses in lentiviral vector-mediated gene transfer.Cellular immunology · 2019Review
- Phagocytosis-shielded lentiviral vectors improve liver gene therapy in nonhuman primates.Science translational medicine · 2019Article
- Persistence of Integrase-Deficient Lentiviral Vectors Correlates with the Induction of STING-Independent CD8Cell reports · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Lentiviral vector (LV)-mediated gene transfer is a promising method of gene therapy. We previously reported that systemic injection of HIV-based LV triggers a transient inflammatory response. Here, we carried out studies to better characterize this response, and to develop a strategy to overcome the adverse effects of interferon (IFN) on LV-mediated gene transfer. We profiled gene expression in the liver after LV administration using deep-sequencing (RNA-seq), and identified several innate response pathways. We examined the response to LV in MyD88-TRIF knockout mice, which are incapable of toll-like receptor (TLR) signaling. Unexpectedly, the IFN response to LV was not reduced in the liver indicating that a non-TLR pathway can recognize LV in this organ. Indeed, blocking reverse transcription with azidothymidine (AZT) reduced the IFN response only in the liver, suggesting that proviral DNA can be a trigger. To block the inflammatory response, we pretreated mice with a short course of dexamethasone (Dex). At 4 hours post-treatment, all the IFN-induced genes were normalized. By blocking the inflammatory response, hepatocyte transduction was dramatically increased, which in turn doubled the level of human factor IX (FIX) produced by a hepatocyte-specific LV. Our studies uncover new insights into LV-induced immune responses in the liver, and provide a means to increase the safety and efficiency of LV-mediated gene transfer.
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