Liposomal particles, methods of making same and uses thereof
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-009/127
A61K-048/00
C12N-015/113
C12N-015/11
출원번호
US-0101523
(2014-12-03)
등록번호
US-10182988
(2019-01-22)
국제출원번호
PCT/US2014/068429
(2014-12-03)
국제공개번호
WO2015/126502
(2015-08-27)
발명자
/ 주소
Mirkin, Chad A.
Nguyen, Sonbinh T.
Banga, Resham Singh
Chernyak, Natalia
Gryaznov, Sergei
Radovic-Moreno, Aleksandar
Mader, Christopher
출원인 / 주소
NORTHWESTERN UNIVERSITY
대리인 / 주소
Marshall, Gerstein & Borun LLP
인용정보
피인용 횟수 :
0인용 특허 :
114
초록▼
Liposomes termed as small unilamellar vesicles (SUVs), can be synthesized in the 20-50 nm size range, but encounter challenges such as instability and aggregation leading to inter-particle fusion. This limits their use as a therapeutic delivery agent. Increasing the surface negative charge of SUVs,
Liposomes termed as small unilamellar vesicles (SUVs), can be synthesized in the 20-50 nm size range, but encounter challenges such as instability and aggregation leading to inter-particle fusion. This limits their use as a therapeutic delivery agent. Increasing the surface negative charge of SUVs, via the attachment of anionic entities such as DNA/RNA, increases the colloidal stability of these vesicles. Additionally, the dense spherical arrangement and radial orientation of nucleic acids exhibits unique chemical and biological properties, unlike their linear counterparts. These liposomal particles, are non-toxic and though anionic, can efficiently enter cells without the aid of ancillary cationic transfection agents in a non-immunogenic fashion. These exceptional properties allow their use as delivery agents for gene regulation in different therapies and offer an alternative platform to metal core spherical nucleic acids.
대표청구항▼
1. A method of inhibiting expression of a gene comprising the step of hybridizing a polynucleotide encoding said gene product with one or more oligonucleotides complementary to all or a portion of said polynucleotide, said oligonucleotide being attached to a liposomal particle, said liposomal partic
1. A method of inhibiting expression of a gene comprising the step of hybridizing a polynucleotide encoding said gene product with one or more oligonucleotides complementary to all or a portion of said polynucleotide, said oligonucleotide being attached to a liposomal particle, said liposomal particle having a substantially spherical geometry, said liposomal particle comprising: a lipid bilayer comprising a plurality of lipid groups; andan oligonucleotide, wherein hybridizing between said polynucleotide and said oligonucleotide occurs over a length of said polynucleotide with a degree of complementarity sufficient to inhibit expression of said gene product. 2. The method of claim 1 wherein expression of said gene product is inhibited in vivo. 3. The method of claim 1 wherein said liposomal particle has a diameter about less than or equal to 50 nanometers. 4. The method of claim 1 wherein said oligonucleotide comprises RNA or DNA. 5. The method of claim 4 wherein said RNA is a non-coding RNA. 6. The method of claim 5 wherein said non-coding RNA is an inhibitory RNA (RNAi). 7. The method of claim 6 wherein the RNAi is selected from the group consisting of a small inhibitory RNA (siRNA), a single-stranded RNA (ssRNA) that forms a triplex with double stranded DNA, and a ribozyme. 8. The method of claim 5 wherein the RNA is a microRNA. 9. The method of claim 4 wherein said DNA is antisense-DNA. 10. The method of claim 1 wherein said plurality of lipid groups comprises a lipid selected from the group consisting of the phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine family of lipids. 11. The method of claim 10 wherein said lipid is selected from the group consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dimyristoyl-sn-phosphatidylcholine (DMPC), 1-palmitoyl-2-oleoyl-sn-phosphatidylcholine (POPC), 1,2-distearoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DSPG), 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-di-(9Z-octadecenoyI)-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dihexadecanoyl-sn-glycero-3- phosphoethanolamine (DPPE). 12. The method of claim 1 wherein the oligonucleotide is an oligonucleotide-lipid conjugate containing a lipophilic tethered group, wherein said lipophilic tethered group is adsorbed into the lipid bilayer. 13. The method of claim 12 wherein the lipophilic tethered group comprises tocopherol or cholesterol. 14. The method of claim 13 wherein tocopherol is chosen from the group consisting of a tocopherol derivative, alpha-tocopherol, beta-tocopherol, gamma-tocopherol and delta-tocopherol. 15. The method of claim 1 wherein the particle comprises from about 10 to about 80 oligonucleotides. 16. The method of claim 15 wherein the particle comprises 70oligonucleotides. 17. The method of claim 1 wherein the gene is a toll-like receptor (TLR). 18. The method of claim 17 wherein said toll-like receptor is chosen from the group consisting of toll-like receptor 1, toll-like receptor 2, toll-like receptor 3, toll-like receptor 4, toll-like receptor 5, toll-like receptor 6, toll-like receptor 7, toll-like receptor 8, toll-like receptor 9, toll-like receptor 10, toll-like receptor 11, toll-like receptor 12, and toll-like receptor 13.
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