162. tweaking the immune system: targeted fusogenic nanoparticles for immunogene therapy against bacterial infection

Department: Mechanical & Aerospace Engineering
Research Institute Affiliation: Graduate Program in Materials Science and Engineering
Faculty Advisor(s): Michael Sailor
Award(s): Rudee Outstanding Award | Department Best Poster

Primary Student
Name: Byungji Kim
Email: byk022@ucsd.edu
Phone: 858-232-8020
Grad Year: 2019

Abstract
Deep-tissue Staphyloccocus aureus infection remains one of the most difficult therapeutic challenges today. With increasing side-effects and resistance developments using small molecule antibiotics, there have been rising focus on immunogene therapy to harness the existing immune system's efforts to clear the infection, and altering it to improve healing efficiency. However, in vivo gene delivery remains a challenge due to low efficiency, deficient specificity, and potential cytotoxicity. Cellular endocytosis is the primary uptake pathway, which results in extracellular excretion and lysosomal degradation of genetic material, leading to low therapeutic efficacy. Herein, we present macrophage-targeted fusogenic liposome-coated porous silicon nanosystem that bypasses endocytosis to achieve potent gene knockdown efficacy. Furthermore, in vivo targeting to macrophages was successfully demonstrated, and the payload-delivered macrophage homed effectively to infected lungs. With siIRF5 delivery to the macrophages to knockdown the pro-inflammatory macrophage marker, IRF5, we found that targeted fusogenic system achieves exceptionally therapeutic immunogenic clearance of infection.

Industry Application Area(s)
Life Sciences/Medical Devices & Instruments | Materials

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