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Sep 25 2020

9/25 – Young Jik Kwon, University of California, Irvine

September 25, 2020

12:00 PM - 1:00 PM


Chicago, IL

Watch this webinar live with Zoom>>

Title: Viral/Nonviral Chimeric Gene Carriers and Chemically Induced Extracellular Blebs (EBs) for Efficient, Safe, and Versatile Cancer Therapies

Abstract: An emerging therapy for highly challenging diseases such as cancers and degenerative neurological diseases requires a capability of effectively, specifically, and precisely manipulating the highly complex processes underlying in disease development and progress. Multi-modal therapy overcomes the limitations of narrowly defined single-modal therapies and is a promising approach to synergistic, targeted, and safe therapeutic outcomes. However, this strategy requires novel platforms encompassing the highly complex demands in compressive functions. Most gene therapies tackle a single pathway, resulting in limited efficiency and making it an ancillary treatment option or approved for rare indications. In this study, adeno-associated virus (AAVs), on which recently approved gene therapy drugs are based, were engineered to encode an apoptotic BIM and further shelled with a MCL-1 siRNA-encapsulating, acid-degradable polymeric layer for avoided immunogenicity during circulation, simultaneous BIM expression and MCL-1 silencing in the target cell, and facilitated eradication of leukemia cells in vitro and in vivo. The same approach is also turned out to be effective against a broad range of cancers such as myeloproliferative neoplasm and non-small cell lung cancer. The extremely high heterogeneity both in physical structure and biological function extracellular vesicles (EVs) and substantially limited scalability for production have been pivotal challenges in the technology. Induction of EVs by chemical and physical triggers allows the efficient and large-scale preparation of highly homogeneous extracellular blebs (EBs). Via sulfhydryl-blocking, EBs in varying sizes were produced and tested for the delivery of cancer chemotherapeutics1 and vaccines. Doxorubicin-encapsulating, nano-sized extracellular blebs (DOX-nEBs) were prepared by an order of magnitude improved production and they were able to eradicate tumors in vivo with minimized off target effects on non-tumorous tissues. Micro-size extracellular blebs carrying a model SIINFEKL antigen (SIINFEKL-µEBs) were also prepared and they generated effective immunity against the tumor that presents the antigen peptide on the surface. This presentation introduces the current status and changes in EV technology, and how a new approach addresses them in putting it a step forward toward potential clinical translation.


Date posted

Sep 1, 2020

Date updated

Oct 16, 2020