DNA, siRNA, miRNA, Oligonucleotides
in vivo functional studies (overexpression, knock-down, CRISPR genome editing)
Various systemic and local administration routes
|Number of injections|
eg. 100 µl of in vivo-jetPEI®-PC delivery reagent is sufficient to perform 15 to 25 intravenous injections in mouse
-20 ± 5 °C, for at least 12 months
10% glucose solution
Animal preclinical studies are a prerequisite for submission of an Investigational New Drug (IND) application to the FDA (USA) or Investigation Medicinal Product Dossier (IMPD) to the EMA (Europe), the mean through which safety and performance of a new drug is reviewed.
Following initial discovery phase with target identification, the focus of preclinical trials in the drug development process is to determine the potency of the Drug product (efficiency, bioavailability, half-life, toxicity), its safety and ease of formulation (chemical stability, solubility). For in vivo preclinical studies, Polyplus-transfection® supplies a ready-to-use preclinical transfection reagent in vivo-jetPEI®-PC equivalent in potency to in vivo-jetPEI®: (Table 1)
Table 1. in vivo-jetPEI® product range is composed of three quality grade in vivo transfection reagents that are directly injectable: Research grade in vivo-jetPEI® for in vivo functional studies and proof of concept studies of nucleic acid mediated therapies; in vivo-jetPEI®-PC for preclinical studies to assess safety, toxicology, and biodistribution; and highest quality grade GMP in vivo-jetPEI® for Human clinical trials.
Polyvalent: Suitable for preclinical animal models
in vivo-jetPEI®-PC, alike in vivo-jetPEI® is extensively used for in vivo transfection of nucleic acids in mouse models using various local and systemic administration routes. Due to the simplicity of nucleic-acid/reagent formulation (see two-step protocol here), in vivo transfection of nucleic acids has been successfully performed in other small rodent animal models (rat, guinea pig, hamster, etc…), larger animal models (dog, cat, sheep, goat, etc…) and up to non-human primate models for preclinical trial studies.
Please contact the dedicated in vivo Scientific Support to establish a protocol for your application and animal model.
Safe: no inflammatory response triggered
At the preclinical stage, the safety, biodistribution and pharmacokinetics of the nucleic acid-based therapy is assessed in a wider cohort of the appropriate animal model (small rodent or larger animal model up to non-human primate). Following in vivo-jetPEI®-PC, alike in vivo-jetPEI® mediated systemic delivery of nucleic acid, there is no induction of major pro-inflammatory cytokines (Figure 1) and no increase in sera levels of hepatic enzymes (Figure 2) (Bonnet et al., 2008).
Figure 1. in vivo-jetPEI® is a safe method of delivery, with no major inflammatory response triggered upon injection. Complexes were formed in 200 µl of 5% glucose using 40 µg of luciferase siRNA with in vivo-jetPEI® at an N/P ratio of 8, and injected through retro-orbital sinus. 1 to 6 hours after injection, blood was collected and the level of TNF, IFN and IL-6 was measured by ELISA (n=8). As a positive control, LPS was injected intraperitoneally.
Figure 2. in vivo-jetPEI® is a safe method of delivery, with no detectable hepatotoxicity. Complexes were formed in 200 µl of 5% glucose using 40 µg of luciferase expressing plasmid with in vivo-jetPEI® at an N/P ratio of 8, and injected through retro-orbital sinus. 24 hours after injection, blood was collected and the level of LDH, ASAT, ALAT and ALP was measured. Each value corresponds to the mean ± SD (n=8). As a positive control, CCl4 was subcutaneously administered.
- Capulli M et ak., (2015) Effective Small Interfering RNA Therapy to Treat CLCN7-dependent Autosomal Dominant Osteopetrosis Type 2. Mol Ther Nucleic Acids 4, e248
- Francis et al., (2014) SNS01-T modulation of eIF5A inhibits B-cell cancer progression and synergizes with bortezomib and lenalidomide. Mol Ther 22, 1643-52
- Campbell M et al., (2012) Targeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury. Nat Commun 3, 849
- Bhang HE et al., (2011) Tumor-specific imaging through progression elevated gene-3 promoter-driven gene expression. Nat Med 17, 123-9
- Amit D et al., (2011) Development of targeted therapy for bladder cancer mediated by a double promoter plasmid expressing diphtheria toxin under the control of IGF2-P3 and IGF2-P4 regulatory sequences. Int J Clin Exp Med 4, 91-102
For further examples of ongoing preclinical trials, refer to the clinical pipeline.
📰 Check out our article on: “Non-viral vector mediated Gene Delivery: the Outsider to Watch out for in Gene Therapy”
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