Breaking Up for Good: Acid-Degradable Nanoparticles for Nonviral Gene Delivery
소속 :
연사 : Prof. Young Jik Kwon (The University of California)
일시 : 2009-09-02 11:00 ~
장소 : 500동 목암홀
일시: 2009년 9월 2일 오전 11:00
장소: 500동 목암홀
-Abstract-
Genetic materials are promising therapeutics and tools to study and control biological phenomena. Gene delivery using synthetic nanomaterials (i.e., nonviral gene delivery) provides a number of advantages over viral vectors, including low immunogenicity and functional flexibility. Among many extracellular and intracellular obstacles in nonviral gene delivery, endosomal escape and localization of delivered genes in their intracellular targets are of highly challenging demands. In addition, efficient dissociation of nucleic acids from delivery carriers is indispensible. Acid-degradable polymers such as ketalized polyethylenimine (K-PEI) efficiently complex plasmid DNA and siRNA as nanoparticles. In vitro experiments demonstrated that nucleic acids were efficiently dissociated from the acid-degradable polyplexes in the endosomal pH and efficiently processed for DNA transfection and RNA interference, with almost completely abolished cytotoxicity. It was also demonstrated that controlled therapeutic effects can be obtained by selective intracellular localization of various nucleic acids using differentially tailored polymers. Another type of acid-degradable cationic nanoparticles was synthesized using in situ polymerization of plasmid DNA with acid-degradable cationic monomers (i.e., monomer-to-polymer approach), which enabled highly flexible nanoparticle fabrications to achieve controlled size, surface charge, degradability, and conjugation with functional groups. Structure of the nanoparticles, efficient release of plasmid DNA upon hydrolysis of the nanoparticles, and enhanced transfection efficiency at a very low DNA concentration was confirmed by nanoparticle characterizations and in vitro studies. A selective uptake of the nanoparticles by phagocytic cells (e.g., macrophages) and non-phagocytic cells (e.g., fibroblasts) was also achieved, which implies tunable gene therapy and DNA vaccination using the nanoparticle system. Preliminary pulmonary transfection and in vivo GFP silencing in a tumor using acid-degradable polyplexes and nanoparticles were also achieved. Overall, this talk will convey how to rationally design stimuli-responsive materials and to overcome challenges in biological and medical research at various scales using inter-, multi-, and transdisciplinary approaches.
장소: 500동 목암홀
-Abstract-
Genetic materials are promising therapeutics and tools to study and control biological phenomena. Gene delivery using synthetic nanomaterials (i.e., nonviral gene delivery) provides a number of advantages over viral vectors, including low immunogenicity and functional flexibility. Among many extracellular and intracellular obstacles in nonviral gene delivery, endosomal escape and localization of delivered genes in their intracellular targets are of highly challenging demands. In addition, efficient dissociation of nucleic acids from delivery carriers is indispensible. Acid-degradable polymers such as ketalized polyethylenimine (K-PEI) efficiently complex plasmid DNA and siRNA as nanoparticles. In vitro experiments demonstrated that nucleic acids were efficiently dissociated from the acid-degradable polyplexes in the endosomal pH and efficiently processed for DNA transfection and RNA interference, with almost completely abolished cytotoxicity. It was also demonstrated that controlled therapeutic effects can be obtained by selective intracellular localization of various nucleic acids using differentially tailored polymers. Another type of acid-degradable cationic nanoparticles was synthesized using in situ polymerization of plasmid DNA with acid-degradable cationic monomers (i.e., monomer-to-polymer approach), which enabled highly flexible nanoparticle fabrications to achieve controlled size, surface charge, degradability, and conjugation with functional groups. Structure of the nanoparticles, efficient release of plasmid DNA upon hydrolysis of the nanoparticles, and enhanced transfection efficiency at a very low DNA concentration was confirmed by nanoparticle characterizations and in vitro studies. A selective uptake of the nanoparticles by phagocytic cells (e.g., macrophages) and non-phagocytic cells (e.g., fibroblasts) was also achieved, which implies tunable gene therapy and DNA vaccination using the nanoparticle system. Preliminary pulmonary transfection and in vivo GFP silencing in a tumor using acid-degradable polyplexes and nanoparticles were also achieved. Overall, this talk will convey how to rationally design stimuli-responsive materials and to overcome challenges in biological and medical research at various scales using inter-, multi-, and transdisciplinary approaches.
