Lipid membrane structure for intracellular delivery of siRNA

Patent metadata

Field	Value
Publication number	US-10182987-B2
Application number	US-201515311644-A
Country	US
Kind code	B2
Filing date	May 18, 2015
Priority date	May 20, 2014
Publication date	Jan 22, 2019
Grant date	Jan 22, 2019

Abstract

A lipid membrane structure encapsulating an siRNA inside thereof and containing a lipid compound of the formula (I) as a lipid component (R1 and R2 represent CH3—(CH2)n—CH═CH—CH2—CH═CH—(CH2)m—, 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 R3 and R4 represent a C1-4 alkyl group or a C2-4 alkenyl group.

First claim

What is claimed is:

1. A lipid compound represented by the following formula (I), or a salt thereof:

wherein, in the formula, R 1 and R 2 independently represent CH 3 —(CH 2 ) n —CH═CH—CH 2 —CH═CH—(CH 2 ) m — (n represents an integer of 3 to 5, and m represents an integer of 6 to 10), p represents an integer of 2 to 7, and R 3 and R 4 independently represent a C 1-4 alkyl group or a C 2-4 alkenyl group.

2. The lipid compound or a salt thereof according to claim 1 , wherein n is 4, m is an integer of 7 to 9, p is an integer of 3 to 5, and R 3 and R 4 are independently C 1-4 alkyl groups.

3. The lipid compound or a salt thereof according to claim 1 , wherein R 1 and R 2 are the same, n is 4, m is 8, p is 4, and R 3 and R 4 are methyl groups.

4. A method for delivering an siRNA intracellularly into a cell comprising intracellularly administering the siRNA together with a lipid membrane structure comprising the lipid compound or a salt thereof according to claim 1 .

5. A lipid membrane structure for delivering an siRNA intracellularly into a cell, which encapsulates the siRNA inside thereof, and contains the lipid compound according to claim 1 as a lipid component.

6. The lipid membrane structure according to claim 5 , which is a liposome.

7. The lipid membrane structure according to claim 5 , which is used for knocking down a target gene in a dendritic cell.

8. The lipid membrane structure according to claim 7 , which is used for knocking down a target gene in a dendritic cell in an immunotherapy comprising separating and collecting a dendritic cell from a patient, introducing an siRNA intracellularly into the dendritic cell in vitro, and administering the dendritic cell in which the target gene has been knocked down to the patient.

9. The lipid compound or a salt thereof according to claim 1 , wherein R 3 and R 4 both represent CH 3 .

10. The lipid compound or a salt thereof according to claim 1 , wherein R 3 and R 4 both represent CH 3 and p represents an integer of 4.

11. The lipid compound or a salt thereof according to claim 1 , wherein R 3 and R 4 both represent CH 3 , p is 4, R 1 and R 2 are the same and m is 8.

12. The lipid compound or a salt thereof according to claim 1 , wherein R 3 and R 4 independently represent a C 1-2 alkyl group or C 2 alkenyl group.

13. A lipid compound represented by the following formula (I), or a salt thereof:

wherein, in the formula, R 1 and R 2 , which are the same, represent CH 3 —(CH 2 ) n —CH═CH—CH 2 —CH═CH—(CH 2 ) m —, n represents an integer of 3 to 5, m is 8, p is 4, and R 3 and R 4 represent CH 3 , and
wherein the lipid compound is linked to a multifunctional envelope-type nano device (MEND).

14. A method for delivering an siRNA intracellularly into a cell comprising intracellularly administering the siRNA together with a lipid membrane structure comprising the lipid compound or a salt thereof according to claim 13 .

15. A lipid membrane structure for delivering an siRNA intracellularly into a cell, which encapsulates the siRNA inside thereof, and contains the lipid compound according to claim 13 as a lipid component.

16. The lipid membrane structure according to claim 15 , which is a liposome.

17. The lipid membrane structure according to claim 15 , which is used for knocking down a target gene in a dendritic cell.

18. The lipid membrane structure according to claim 17 , which is used for knocking down a target gene in a dendritic cell in an immunotherapy comprising separating and collecting a dendritic cell from a patient, introducing an siRNA intracellularly into the dendritic cell in vitro, and administering the dendritic cell in which the target gene has been knocked down to the patient.

19. The lipid compound or salt thereof according to claim 1 , wherein R 3 and R 4 independently represent a C 1-2 alkyl group.

Assignees

• Univ Hokkaido Nat Univ Corp

Inventors

• Harashima Hideyoshi
• Sato Yusuke
• WARASHINA Shota
• Hatakeyama Hiroto
• Hyodo Mamoru
• Nakamura Takashi

Classifications

• A61K9/12 Primary

  Aerosols; Foams {(A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015)} · CPC title

• A61K47/6917

  the form being a lipoprotein vesicle, e.g. HDL or LDL proteins · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• C07C215/08

  with only one hydroxy group and one amino group bound to the carbon skeleton · CPC title