Hokkaido University

Nof Corporation

Japan Science and Technology Agency

University of Tsukuba

Luca Science Inc.

Nitto-denko Corporation

Shionogi Company Limited

Nagoya University

Taiho Pharmaceutical Company Limited

Kewpie Corporation

Japan Bcg Laboratory

Hideyoshi Harashima

Hidetaka Akita

Yusuke Sato

Kota Tange

Kentaro Kogure

Hiroto Hatakeyama

Yuta Nakai

Shiroh Futaki

Takashi Nakamura

Kazuhiro Kubo

Manabu Tokeshi

Hiroki Tanaka

Masatoshi Maeki

Mamoru Hyodo

Naoya Miura

Takuya Shishido

Masaya Arai

Yoshinobu Baba

Yoshiki Maeda

Hiroyuki Tsuchiya

Noritada Kaji

Hideyuki Akaza

Masamitsu Taguchi

Sachiko Sakamoto

Masaki Ota

Nobuhiro Ohkohchi

Shota Sasaki

Kenji Kusumoto

Shinji Chaki

Masami Ukawa

Yasuo Shinohara

Hiroshi Kuramoto

Takahiro Fujiwara

Arisa Minoura

Takuya Ishikawa

Yuma Yamada

Daisuke Sasaki

Takafumi Yokota

Masashi Suganuma

Kazuki Hashiba

Ayaka Otsu

Mohammad Shaheen Sharif

Ayaka Watanabe

Naoyuki Toriyabe

Takafumi Tamura

Naoki Sano

Ryohei Togashi

Mio Maeta

Shota Warashina

Yuki Noguchi

Masafumi Fukiage

Megumi Higuchi

Jun Miyazaki

Akihiro Nakaya

Ryohei Ishiba

Taichi Ishitsuka

Soichiro Ishii

Nayuta Shimizu

Hiroyuki Kamiya

The present invention addresses the problem of providing lipid nanoparticles which function as gene transfer carriers capable of selective transfer to the liver or spleen. Lipid nanoparticles which contain a pH-sensitive cationic lipid represented by formula (I) [a represents an integer of 3-5; b represents 0 or 1; Rand Reach independently represent a group represented by general formula (A) (Rand Reach independently represent a linear or branched Calkyl group; c represents 0 or 1; v represents an integer of 4-12); and X represents a group represented by general formula (B)(d represents an integer of 0-3; and Rand Reach independently represent a Calkyl group or Calkenyl group, while Rand Rmay form a 5- to 7-membered non-aromatic heterocycle) or represents a 5- to 7-membered non-aromatic heterocyclic group]. (I) (R)(R)C(OH)—(CH)a-(O—CO)b-X. (A): (R)(R)—CH—(CO—O)c-(CH)v-. (B):—(CH)d-N(R)(R).(R)(R)C(OH)—(CH)—(O—CO)-X  (I)(R)(R)—CH—(CO—O)—(CH)-  (A)—(CH)-N(R)(R)  (B)

Lipid nanoparticle

The present invention addresses the problem of providing a lipid nanoparticle in which a nucleic acid, etc., required in genome editing is encapsulated and which can be produced by an alcohol dilution method using flow channels and contributes to high genome editing efficiency. The present invention pertains to a lipid nanoparticle which comprises a lipid component, a DNA nuclease, a guide RNA and a single-stranded oligonucleotide, wherein: the lipid component comprises a pH-sensitive cationic lipid, a neutral phospholipid and a polyalkylene glycol-modified lipid; the ratio of the pH-sensitive cationic lipid relative to the total lipids constituting the lipid nanoparticle is 30-50 mol %; the ratio of the neutral phospholipid relative to the total lipids constituting the lipid nanoparticle is 20-50 mol %; and the ratio of the polyalkylene glycol-modified lipid relative to the total lipids constituting the lipid nanoparticle is 1-4 mol %.

Provided are: a flow channel structure with which lipid particles or micelles, which are useful as nano-sized carriers, for example, in drug delivery systems, are produced with good control of particle size; and a method for forming lipid particles or micelles using the same. Said flow channel structure has a two-dimensional structure such as one in which multiple structural elements (baffles) of a specified width are alternately disposed from the two side faces in a micro-sized flow channel through which feedstock solutions are flowed.

Flow channel structure and lipid particle or micelle formation method using same

Provided herein are a method for isolation and transplantation of intact mitochondria to a lymphoid organ (a primary lymphoid tissue or a secondary lymphoid tissue), a composition of cells prepared by using a method described herein, and a method for manufacturing cells described herein. In particular, provided herein are methods of isolating intact mitochondria from a donor cell. Also provided herein are methods of transplanting mitochondria into a recipient cell. In some aspects, the methods can be performed in vivo. Further provided are a composition of cells that include the cells prepared using the methods of the present invention.

Transplantation of mitochondria into lymphoid organ and composition therefor

The problem to be solved is to provide a novel expression vector capable of effectively expressing a target protein in mitochondria and suppressing undesirable expression of the target protein in cell organelles other than mitochondria. The present invention provides a recombinant expression vector for expressing a target protein in mitochondria of animal cells, and a lipid membrane structure having the vector encapsulated therein, wherein the recombinant expression vector has a promoter sequence exhibiting a transcription activity in the nuclei of animal cells, and has, under the control of the promoter sequence, a coding region which codes a target protein and includes one or more TGAs as codons corresponding to tryptophan. The recombinant expression vector according to the present invention can more efficiently and selectively express a target protein in mitochondria, and can be used as a more safe and effective drug for treating mitochondrial diseases.

Recombinant expression vector and lipid membrane structure having said vector encapsulated therein

A lipid membrane structure includes, as lipid components, a lipid compound represented by Formula (I):(R)(R)C(OH)&#x2014;(CH)&#x2014;(O&#x2014;CO)&#x2014;X&#x2003;&#x2003;(I)

Lipid membrane structure for delivery into siRNA cell

The present invention provides an O/W type emulsion having a volume median diameter of not more than 100 nm and containing a compound represented by the formula (1) wherein Xand Xare each independently X, Xor a 1,4-piperazinediyl group; s is 1 or 2,Ris an alkyl group having 1-6 carbon atoms,nand nare each independently 0 or 1,R, R, Rand Rare each independently an alkylene group having 1-6 carbon atoms,Yand Yare each independently an ester bond, or the like, andRand Rare each independently a liposoluble vitamin residue or the like.

O/W type emulsion

Hyaluronic acid modified with sphingosine-1-phosphate, and a medicine comprising the hyaluronic acid as an active ingredient, wherein the medicine can alleviate hepatic disorder caused by hypoxia/reoxygenation by protecting the liver sinusoidal endothelial cells, and the medicine can prevent and/or treat liver failure due to liver transplantation, hepatectomy, or other surgeries associated with liver ischemia/reperfusion.

Hyaluronic acid modified by sphingosine-1-phosphoric acid

The present invention aims to provide a cationic lipid that can be used as a nucleic acid delivery carrier, a lipid membrane structure using a cationic lipid, a nucleic acid-introducing agent using a cationic lipid, and a method of achieving nucleic acid introduction by using a nucleic acid-introducing agent containing a cationic lipid. A lipid membrane structure containing a cationic lipid represented by the formula (1) wherein each symbol is as defined in the DESCRIPTION, is superior in the stability in blood and tumor accumulation property. A nucleic acid-introducing agent using the cationic lipid can achieve high nucleic acid delivery efficiency of nucleic acid to be delivered into the cytoplasm.

Cationic lipid

A lipid membrane structure encapsulating an siRNA inside thereof and containing a lipid compound of the formula (I) as a lipid component (Rand Rrepresent CH&#x2014;(CH)&#x2014;CH&#x2550;CH&#x2014;CH&#x2014;CH&#x2550;CH&#x2014;(CH)&#x2014;, n represents an integer of 3 to 5, m represents an integer of 6 to 10, p represents an integer of 2 to 7, and Rand Rrepresent a Calkyl group or a Calkenyl group.

Lipid membrane structure for intracellular delivery of siRNA

The invention provides a cationic lipid capable of achieving higher intracellular delivery efficiency than conventional cationic lipids, when used as a lipid membrane structure which is a carrier for delivering functional nucleic acid. The cationic lipid is represented by the formula (1): 

Cationic lipid for nucleic acid delivery

[Problem] To provide: a lipid membrane structure which has such a particle diameter that the lipid membrane structure can be sterilized by filtration, contains a lipid that is bound to a peptide composed of multiple arginine residues as a constituent lipid, and includes a bacterial cell component having dispersibility in a non-polar solvent; and a method for producing a lipid membrane structure which has such a particle diameter that the lipid membrane structure can be sterilized by filtration and includes a substance of interest having dispersibility in a non-polar solvent. [Solution] A lipid membrane structure which has such a particle diameter that the lipid membrane structure can be sterilized by filtration, contains a lipid that is bound to a peptide composed of multiple arginine residues as a constituent lipid, and includes a bacterial cell component having dispersibility in a non-polar solvent.

Lipid membrane structure including bacterial cell component having dispersibility in non-polar solvent, and method for producing same

The present invention relates to a compound represented by the formula (1) wherein Xand Xare each independently Xor X; s is 1 or 2,Ris an alkyl group having 1-6 carbon atoms,nand nare each independently 0 or 1,Rand Rare each independently an alkylene group having 1-6 carbon atoms,Rand Rare each independently an alkylene group having 1-6 carbon atoms,Yand Yare each independently an ester bond, an amide bond, a carbamate bond, an ether bond or a urea bond, andRand Rare each independently a sterol residue, a liposoluble vitamin residue or an aliphatic hydrocarbon group having 12-22 carbon atoms,and use thereof.

Cationic lipid having improved intracellular kinetics

The present invention provides a liposome having excellent lung migration ability that had not existed hitherto, by including GALA or Chol-GALA in the liposome. Furthermore, by using the liposome, a pulmonary delivery carrier having a stronger knockdown effect of siRNA when compared to existing carriers is provided.

Vector for pulmonary delivery, inducing agent, and uses

A lipid membrane structure for delivering a substance into a nucleus of a cell, wherein lipid membrane is modified with (a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and/or (b) a polypeptide consisting of an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 1, but including deletion and/or substitution and/or insertion of one or several amino acid residues, and having an activity of promoting migration of the lipid membrane structure into a nucleus of a cell, which can efficiently deliver a nucleic acid into a nucleus of an immunocyte such as dendritic cell.

Lipid membrane structure having intranuclear migrating property

Growing community of inventors

Sapporo, Japan

Hideyoshi Harashima