World Drug Delivery Summit

Biography

Biography: Hidetaka Akita

Abstract

A category of biomedicine is now expanding from low-molecular drugs to the recombinant protein, antibody, and nucleic acids (i.e. siRNA, mRNA and plasmid DNA). While the gene therapy approach has faced technical and/or regulatory impediments, a large number of clinical trials are still ongoing worldwide. One crucial success is the first approval of the Glybera® (UniQure) by the European Medicinal Agency (EMA) as a first gene-based medication\\r\\nGene expression efficacy is rate-limited by the multiple processes (i.e. cellular uptake, endosomal escape, cytoplasmic transport and nuclear delivery). Adequate design to overcome these barriers is a minimum requirement. Our quantitative and mechanism-based information on differences in transfection efficiency between viral and artificial cationic vectors revealed that post-nuclear delivery processes (i.e. transcription and translation) predominantly contributed to the poor transfection efficacy in artificial ones in dividing cells. In other words, the process of the post-organelle delivery process (intra-organelle disposition) should be taken into the consideration.\\r\\nIn this presentation, I’ll propose two strategies to enhance/maximize these processes. First strategy is to develop a neutral nanoparticle in those the use of the cationic material is minimized. As an example, I’ll focus on the concept of SS-cleavable and pH-activated lipid-like materials (ssPalm), that are designed to collapse in response to the intracellular environment to accelerate the “decapsulation/release” of nucleic acids (DNA and siRNA). \\r\\nAs another strategy, I’ll propose a particle that mounts a “Switch-on” function as a trigger of signal transduction, and stimulation of transcription. As an example, I’ll summarize the dendritic cell-targeted gene delivery for the DNA vaccine.\\r\\n\\r\\n