Summary
in vivo-jetPEI® is the leading in vivo delivery method with a proven track record of over 700 publications. in vivo-jetPEI® is an injectable polymer-based in vivo transfection reagent that was developed with the following objectives: easiness of use, efficiency and versatility. It is a cationic polymer composed of PEI that efficiently encapsulates and protects nucleic acids by forming less than 100 nm nanoparticles that efficiently penetrate in the tissue to reach targeted cells.
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 safety, toxicology, and biodistribution studies; and highest quality grade GMP in vivo-jetPEI® for Human clinical trials (Table 1).
Table 1: Range of in vivo-jetPEI® quality grade reagents for each step of nucleic acid-mediated non-viral vector-based manufacturing. in vivo-jetPEI® is available as an R&D grade for fundamental research and proof of concept studies. For preclinical biodistribution and toxicology studies and early phase clinical studies, we supply a higher preclinical grade in vivo-jetPEI®. GMP in vivo-jetPEI® is the highest quality grade available to meet quality demands in Human clinical trials.
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“Non-viral vector mediated Gene Delivery: the Outsider to Watch out for in Gene Therapy”
Suitable for in vivo delivery of DNA, si/sh/miRNA nucleic acids
in vivo-jetPEI® is the in vivo transfection reagent of choice that offers a panel of possibilities to perform in vivo silencing or expression studies with its ability to deliver any type of nucleic acid (DNA, siRNA, miRNA, etc.) using most frequent administration routes (intravenous, intramuscular, subcutaneous, intraperitoneally), as well as many others including intracerebral, intratumoral, topical application and nasal instillation (Fig. 1).
Fig. 1: Example of mice administration routes using in vivo-jetPEI®.
In addition to in vivo-jetPEI®, we have developed in vivo-jetPEI® derivatives to further enhance in vivo delivery to specific cell types:
– in vivo-jetPEI®-Gal corresponds to galactose-conjugated in vivo-jetPEI® designed to enhance in vivo transfection of cells expressing galactose-specific membrane lectins, such as hepatocytes bearing the asialoglycoprotein receptor (ASGP-R or Gal/GalNAc receptor).
– in vivo-jetPEI®-Man corresponds to mannose-conjugated in vivo-jetPEI® designed to enhance in vivo transfection of cells expressing mannose-specific membrane receptors, such as macrophages and dendritic cells.
Safe and injectable from proof of concept studies up to Human clinical trials
in vivo-jetPEI® has been selected as the in vivo transfection vector of choice for the development of a growing number of nucleic acid-mediated therapies, due to its safety, reliability and delivery efficiency. in vivo-jetPEI® is currently used for in vivo delivery of nucleic acids in several ongoing Phase I, II and III clinical trials for gene therapy treatments of cancer (e.g. pancreatic, bladder), traumatic brain injury and HIV immune gene therapy (Fig. 2).
Fig. 2: Clinical pipeline of ongoing clinical trials using cGMP in vivo-jetPEI® delivery reagent.
Citations
Acosta, C., Djouhri, L., Watkins, R., Berry, C., Bromage, K., Lawson, S. N. (2014). TREK2 expressed selectively in IB4-binding C-fiber nociceptors hyperpolarizes their membrane potentials and limits spontaneous pain., J Neurosci 34, 1494-509.
Buscail, L., Bournet, B., Vernejoul, F., Cambois, G., Lulka, H., Hanoun, N., Dufresne, M., Meulle, A., Vignolle-Vidoni, A., Ligat, L., Saint-Laurent, N., Pont, F., Dejean, S., Gayral, M., Martins, F., Torrisani, J., Barbey, O., Gross, F., Guimbaud, R., Otal, P., Lopez, F, Tiraby, G. and Cordelier, P. (2015). First-in-man Phase 1 Clinical Trial of Gene Therapy for Advanced Pancreatic Cancer: Safety, Biodistribution, and Preliminary Clinical Findings., Mol Ther 23, 779-89.
Ellermeier, J., Wei, J., Duewell, P., Hoves, S., Stieg, M. R., Adunka, T., Noerenberg, D., Anders, H. J., Mayr, D., Poeck, H., Hartmann, G., Endres, S., Schnurr, M. (2013). Therapeutic efficacy of bifunctional siRNA combining TGF-beta1 silencing with RIG-I activation in pancreatic cancer., Cancer Res 73, 1709-20.
Wahlquist, C., Jeong, D., Rojas-Munoz, A., Kho, C., Lee, A., Mitsuyama, S., van Mil, A., Park, W. J., Sluijter, J. P., Doevendans, P. A., Hajjar, R. J., Mercola, M. (2014). Inhibition of miR-25 improves cardiac contractility in the failing heart., Nature 508, 531-5.
Zuckermann, M., Hovestadt, V., Knobbe-Thomsen, C.B., Zapatka, M., Northcott, P.A., Schramm, K., Belic, J., Jones, D.T.W., Tschida, B., Moriarity, B., Largaespada, D., Roussel, M.F., Korshunov, A., Reifenberger, G., Pfister, S.M., Lichter, P., Kawauchi, D. and Gronych, J. (2015). Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling., Nat Commun 6:7391.
Testimonials
« I finished the experiments and I think in vivo-jetPEI works great. I am very pleased with the results. Actually some of the work we have done with in vivo-jetPEI® as well as jetSI™ 10 mM has been published in Science. I would like to tell you that I am also very pleased with the technical assistance. Many thanks! » – E.E.K., Hacettepe Univeristy, Turkey
« Our project is going quite well, we are working a lot with your siRNAs delivery system, and we are obtaining superb results in vivo. » – M.C., L’Aquila University, Italy
« We did a preliminary trial with in vivo-jetPEI® and a luciferase construct delivered into the ventricle of a cannulated mouse and it worked great! » – C.M., University of Minnesota, United States