Development of Small, Homogeneous pDNA Particles Condensed with Mono-cationic Detergents and Encapsulated in a Multifunctional Envelope-type Nano Device(Biopharmacy)
スポンサーリンク
概要
- 論文の詳細を見る
Non-viral DNA vectors are promising gene delivery systems and a variety of non-viral DNA vectors have been developed to date. Recently, we developed a novel non-viral gene delivery system-multifunctional envelope-type nano device (MEND). The MEND system has high transfection activity, similar to that of adenovirus vector, which is a potent viral vector. However, conventional MEND is relatively large and heterogeneous (approximately 300 nm), probably because they contain relatively large- and heterogeneous-pDNA particles condensed with polycations, such as poly-L-lysine. Small particle size is important for in vivo delivery, because large particles are rapidly eliminated from systemic circulation. Moreover, heterogeneous size of drug carriers is difficult to apply to clinical applications. Here, we describe construction of small homogeneous MEND. First, we screened mono-cationic detergents (MCD(s)) to obtain optimal pDNA condensed particles. We determined that benzyldimethylhexadecylammonium chloride (BDHAC) and thonzonium bromide (TB) were optimal pDNA condensers. Next, we packaged the condensed pDNA particles into a lipid bi-layer. The resulting lipid-encapsulated pDNA particles were then equipped with octaarginine to facilitate cell-uptake (R8-MEND (MCD)). The carrier showed high transfection activity in cultured HeLa cells. Furthermore, the R8-MEND (MCD) were small and homogeneous compared with conventional MEND. These results indicate that R8-MEND (MCD) has potential as a novel non-viral delivery system for clinical application.
- 公益社団法人日本薬学会の論文
- 2008-06-01
著者
-
Yamada Yuma
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
-
Yamada Yuma
Laboratory For Molecular Design Of Pharmaceutics Faculty Of Pharmaceutical Sciences Hokkaido Univers
-
Suzuki Ryosuke
Laboratory For Molecular Design Of Pharmaceutics Faculty Of Pharmaceutical Sciences Hokkaido Univers
-
HARASHIMA Hideyoshi
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido Unive
-
Harashima Hideyoshi
Laboratory For Molecular Design Of Pharmaceutics Faculty Of Pharmaceutical Sciences Hokkaido Univers
-
山田 勇磨
北海道大学大学院薬学研究科薬剤分子設計学分野
-
HARASHIMA Hideyoshi
Laboratory for Molecular Design of Pharmaceutics and COE Program in the 21st Century, Graduate School of Pharmaceutical Sciences, Hokkaido University
関連論文
- Transgene expression efficiency from plasmid DNA delivered as a complex with histone H3
- Comparison between a Multifunctional Envelope-Type Nano Device and Lipoplex for Delivery to the Liver
- 多機能性エンベロープ型人工遺伝子デリバリーシステムの創製
- 多機能性エンベロープ型ナノ構造体による人工遺伝子デリバリーシステムの創製 : 第7回日本DDS学会永井賞受賞によせて
- 多機能性エンベロープ型ナノ構造体(MEND)を用いたタンパク質の効率的な細胞質送達
- MITO-Porter : a liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion
- Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized superoxide dismutase by increasing its cellular uptake
- Development of Small, Homogeneous pDNA Particles Condensed with Mono-cationic Detergents and Encapsulated in a Multifunctional Envelope-type Nano Device(Biopharmacy)
- Efficient Cytoplasmic Protein Delivery by Means of a Multifunctional Envelope-type Nano Device(Biopharmacy)
- The First FIP-APSTJ Joint Workshop on Gene Delivery の報告
- DNA Microarray Analysis of Whole Blood Cells and Insulin-Sensitive Tissues Reveals the Usefulness of Blood RNA Profiling as a Source of Markers for Predicting Type 2 Diabetes
- DNA Microarray Analysis of Type 2 Diabetes-Related Genes Co-regulated between White Blood Cells and Livers of Diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats
- Mitochondrial matrix delivery using MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes
- Development of Efficient Packaging Method of Oligodeoxynucleotides by a Condensed Nano Particle in Lipid Envelope Structure(Biopharmacy)
- Calpain 10 as a Predictive Gene for Type 2 Diabetes : Evidence from a Novel Screening System Using White Blood Cells of Otsuka Long-Evans Tokushima Fatty (OLETF) Rats (Biopharmacy)
- Significant and prolonged antisense effect of a multifunctional envelope-type nano device encapsulating antisense oligodeoxynucleotide
- Genome Wide Expression Analysis of White Blood Cells and Liver of Pre-diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats Using a cDNA Microarray
- Pharmacokinetic Modeling of Species-dependent Enhanced Bioavailability of Trifluorothymidine by Thymidine Phosphorylase Inhibitor
- Mitochondrial drug delivery systems for macromolecule and their therapeutic application to mitochondrial diseases
- Efficient Short Interference RNA Delivery to Tumor Cells Using a Combination of Octaarginine, GALA and Tumor-Specific, Cleavable Polyethylene Glycol System
- Mitochondrial drug delivery and mitochondrial disease therapy--an approach to liposome-based delivery targeted to mitochondria.
- Intranuclear DNA Release Is a Determinant of Transfection Activity for a Non-viral Vector: Biocleavable Polyrotaxane as a Supramolecularly Dissociative Condenser for Efficient Intranuclear DNA Release
- Mitochondrial delivery of mastoparan with transferrin liposomes equipped with a pH-sensitive fusogenic peptide for selective cancer therapy.
- Dual function MITO-Porter, a nano carrier integrating both efficient cytoplasmic delivery and mitochondrial macromolecule delivery.
- Mitochondrial-targeted DNA delivery using a DF-MITO-Porter, an innovative nano carrier with cytoplasmic and mitochondrial fusogenic envelopes
- ミトコンドリアとDDS
- ミトコンドリア標的型Drug Delivery System (DDS) が拓くミトコンドリア創薬への道
- ミトコンドリアを標的とした遺伝子治療に向けて
- MITO-Porter; A Cutting-edge Technology for Mitochondrial Gene Therapy
- S1I-2-4 医療現場で新しい薬剤師職能を開拓する活動(病院オペ室での活動)と教員としての研究教育活動(シンポジウム S1I-2 薬学・薬剤師教育の充実、薬剤師職能の向上、医療薬学の発展のために臨床系・実務家教員は何をすべきか?,岐路に立つ医療〜千年紀の目覚め〜よみがえれ!ニッポン!薬の改革は我らが手で!)
- 膵島移植とミトコンドリア標的型 drug deivery system (DDS)
- Intracellular observation of nanocarriers modified with a mitochondrial targeting signal peptide(BIOMEDICAL ENGINEERING)
- The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors