Hokkaido University · Biochemistry, Genetics and Molecular Biology
히데요시 하라시마 교수의 연구실은 비바이러스 유전자 전달 시스템의 효율성을 극대화하기 위한 나노입자 기반 전달 시스템 개발에 초점을 맞추고 있습니다. 특히 리포좀을 이용한 유전자 및 siRNA의 세포 내 정량적 이동 분석, 엔도좀 탈출 메커니즘 향상, 그리고 종양조직에 대한 정확한 약물 도달을 가능하게 하는 다기능성 나노디바이스(MEND)의 설계와 평가를 핵심 연구 방향으로 삼고 있습니다. 이는 암 치료를 위한 비침습적이고 정밀한 유전자 치료 전략의 실현을 목표로 합니다.
Figures are computed from collected data and may differ slightly.
The present study examines the role of surface modification with an octaarginine peptide (R8) in liposomal escape from endocytic vesicles, using octalysine (K8) as a control cationic peptide; the mechanism of endosomal escape of liposomes was also investigated. Gene expression of condensed plasmid DNA encapsulated in R8-modified nanoparticles was more than 1 order of magnitude higher than that of K8-modified nanoparticles, and 2 orders of magnitude higher than gene expression using unmodified na
Since endosomal escape and the nuclear delivery of plasmid DNA (pDNA) constitute major barriers for transgene expression, a quantitative evaluation of intracellular trafficking of pDNA would be highly desirable in terms of optimizing a nonviral gene delivery system. In the present study, a novel strategy is proposed for the quantification of rhodamine-labeled pDNA in endosomes/lysosomes, cytosol, and nucleus. Endosomes/lysosomes and nucleus were stained with LysoSensor DND-189 and Hoechst 33258,
Small interfering RNA (siRNA) would be predicted to function as a cancer drug, but an efficient siRNA delivery system is required for clinical development. To address this issue, we developed a liposomal siRNA carrier, a multifunctional envelope-type nanodevice (MEND). We previously reported that a MEND composed of a pH-sensitive cationic lipid, YSK05, showed significant knockdown in both in vitro and in tumor tissue by intratumoral injection. Here, we report on the development of an in vivo siR
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