ArticleNucleic acid therapeutics2011
Immune activation and target organ damage are consequences of hydrodynamic treatment but not delivery of naked siRNAs in mice.
Article in Nucleic acid therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Successful liver-directed gene delivery by ERCP-guided hydrodynamic injection (with videos).Gastrointestinal endoscopy · 2018Article
- Characterization of Putative Erythroid Regulators of Hepcidin in Mouse Models of Anemia.PloS one · 2017Article
- Liver-targeted gene therapy: Approaches and challenges.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2015Review
- Fighting against kidney diseases with small interfering RNA: opportunities and challenges.Journal of translational medicine · 2015Review
- The dynamic impact of hydrodynamic gene transfer on the immune system.International journal of clinical and experimental medicine · 2015Article
- Hyperactive piggyBac transposons for sustained and robust liver-targeted gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Article
- An adaptable system for improving transposon-based gene expression in vivo via transient transgene repression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- An inducible transgenic mouse model for immune mediated hepatitis showing clearance of antigen expressing hepatocytes by CD8+ T cells.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Short-interfering RNAs (siRNAs), key mediators of RNA interference comprise a promising therapeutic tool, although side effects such as interferon (IFN) response are still not perfectly understood. Further, delivery to target organs is a major challenge, possibly associated with side effects including immune activation or organ damage. We investigated whether immune activation as a consequence of double-stranded RNA induced IFN response (Jak/STAT pathway activation or cytokine production) or target organ damage is induced by in vivo low-volume (LV) or high-volume (HV) hydrodynamic delivery or treatment with naked siRNA. NMRI mice were injected with naked siRNAs or saline by hydrodynamic injection (HDI) and positive control mice received polyinosinic-polycytidilic acid (poly I:C). LV (1 mL/mouse) and HV (10% of body weight) HDI were compared. After LV HDI, STAT1 and OAS1 gene expression inflammatory cytokine plasma levels and target organ injury were assessed. LV HDI induced slight alanine aminotransferase elevation and mild hepatocyte injury, whereas HV HDI resulted in high ALAT level and extensive hepatocyte necrosis. STAT1 or OAS1 was not induced by LV siRNA; however, HV saline led to a time-dependent slight increase in gene expression. Inflammatory cytokine plasma level and organ histology and functional parameters demonstrated no damage following LV HDI with or without siRNA. Our data demonstrate that naked siRNAs may be harnessed, without the induction of IFN response or immune activation, and that LV HDI is preferable, because HV HDI may cause organ damage.
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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.