Envoya Inc.'s Cell & Gene Therapy Summit 2024 Poster

Abstract:

The success of gene therapy depends on safely and precisely delivering genetic material to target cells, despite biological barriers. Efficient delivery systems must overcome challenges like immune responses, off-target effects, and limited cellular uptake. We successfully have developed Envoyer, biopolymer-based nanoparticles, formulated using external gelation-based microfluidics. Here we present Envoyers’ size consistency, low immunogenicity, and transfection efficacy in vitro and in vivo. Transmission electron microscopy showed Envoyer nanoparticles encapsulating siRNA maintain a consistent size of 20–30 nm in diameter. Envoyer-encapsulating survivin siRNA are internalized by cells and acted in a dose- and time-dependent manner. In PANC1 cells, 62.5 nM of Envoyer-encapsulating survivin siRNA significantly reduced survivin mRNA and protein levels, with higher doses (125 and 250 nM) enhancing the effect. A time course showedreductions in mRNA and protein levels as early as 3 hours post-transfection, continuing for 48 hours. Storage at -80°C did not affect Envoyers’ transfection efficiency and neither did freeze-thaw cycles. Notably, intraperitoneal injection in mice models did not raise inflammatory cytokine levels, indicating Envoyer nanoparticles are non-immunogenic. Intratumoral injection of Envoyer-encapsulating NUF2 siRNA in NOD-SCID gamma mice reduced tumor growth by 60% without affecting body weight. Tumor analysis confirmed successful delivery and target engagement, showing Envoyer nanoparticles are safe and effective in rodent tumor models. These results suggest Envoyer nanoparticles may serve as a stable and efficient gene therapy delivery system.

‍

Conclusion:

Our Envoyer delivery platform is stable and effective in modulating targeted-genetic material using siRNA both in vitro and in vivo. Moreover, this study provides the supportive framework that biopolymer-based nanoparticles can potentially offer many advantages including ease of formulation, increased stability, lower immunogenicity compared to LNP (as shown in the current study) and the ability to easily customize the delivery of targeted information for the treatment-specific diseases.