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GMP-grade transfection reagents

For the development of innovative new therapies based on the use of gene expression vectors, siRNA or miRNAs, there is an urgent need for safe, non-viral, GMP-grade transfection reagents. Therefore, Synvolux has put much effort in optimizing the synthesis, production processes and manufacturing conditions to develop a cost-effective transfection reagent that is readily amenable to high-volume, GMP-grade production for clinical use. One of the unique properties of SAINT lipids that distinguishes it from other lipids, is its heat tolerance (see the picture below).

Currently, heat-sterilized, GMP-grade SAINT lipids are being used in a clinical trial at the Radboud University Medical Center (Nijmegen, the Netherlands) for dendritic cell vaccinations to boost graft-versus-tumor immunity. Preceding work describing the benefits of SAINT lipids for this and other clinical studies is described by Roeven et al.

The specifications of GMP-grade SAINT lipids:

• Purity                          > 96%
• Endotoxin                  < 5 EU/ml
• RNAse activity          < 0.1 mU/ml

Bioburden

• Cetrimide                  < 5 CFU/ml
• R2A                            < 5 CFU/ml
• Sabouraud                < 5 CFU/ml
• Caso                           < 5 CFU/ml
• Endo                          < 5 CFU/ml

* GMP-grade means: Production of the transfection reagent (SAINT-RED) under pharmaceutical conditions. To be approved by EMEA or FDA after inclusion of the active pharmaceutical ingredient (siRNA) delivered by the customer.

GMP-grade SAINT-RED can be heat sterilized without detectable loss of transfection efficacy (transfection of CHO-K1 cells with GFP-encoding plasmid):

SAINT-Vivo enables in vivo transfection and vaccination

SAINT-Vivo is an optimised version of the SAINT-18 cationic lipid, which has been used by several groups of researchers for in vivo application as a delivery agent for DNA.

The group of C.N.Kuo et al. has shown non-inflammatory corneal transfection in rats. In one of their publications they demonstrate inhibition of corneal neovascularization with a plasmid encoding pigment epithelium-derived factor (p-PEDF), delivered by SAINT-18, in an experimental model of rat corneal angiogenesis. Yet another publication examines the combination of a recombinant humanized monoclonal antibody to VEGF with p-PEDF/SAINT-18. Together, this work demonstrates that a combination of antibody and gene therapy using SAINT-18 may have potent and prolonged anti-angiogenic effects, thus providing a potential new therapy for severe complications of ischaemic ocular diseases caused by neovascularisation.

In the field of DNA vaccination, Endmann et al. have shown SAINT-mediated delivery of a gene expression vector coding for hepatitis B virus surface antigen (HBsAg). Upon intradermal injection of this DNA vaccine, a dose-dependent antibody response was elicited in mice. Another publication by the same group demonstrated that when administered in combination with SAINT-18, the expression vector is found in significantly larger amounts in draining lymph nodes compared to the same vector without SAINT-18. Furthermore, the use of SAINT-18 resulted in greater antigen expression, and the combination of SAINT-18 with the gene expression vector was well tolerated in mice and rats. In a study in pigs, Endmann et al. show that a SAINT-18 formulated DNA vaccine at a relatively low dose elicits an immune response similar to a normal dose of a commercial, licensed aluminum hydroxide-adjuvanted protein vaccine. After three vaccinations, the SAINT-18 formulated DNA vaccine induces a specific antibody response at a level considered protective. In conclusion, a SAINT-formulated DNA vaccine may provide a safe and effective alternative to current hepatitis B vaccines.

A research group at the university of Hannover has shown the application of SAINT-18 as a delivery agent in therapeutic DNA vaccination therapy against equine melanoma. Grey horses vaccinated thrice with DNA vectors  encoding equine IL-12 and IL-18 display a significant decrease in tumour burden.

In conclusion, these animal studies demonstrate that SAINT-18 is an excellent delivery vehicle for gene expression vectors for in vivo applications, including DNA vaccines that elicit effective immune responses against viruses and cancer.

MSDS:

• MSDS SAINT-Solid (.PDF)
• MSDS SAINT-Vivo (.PDF)

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