北海道大学 · 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.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
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