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Patent US6436708B1 successfully refreshed from Google Patents.
US6436708B1
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Delivery system for gene therapy to the brain
Assignee: Vector Neurosciences Inc
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Filing: 1998-04-17
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Granted: 2002-08-20
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Expires: 2018-04-17
Abstract
Abstract A gene delivery system which. is both safe and results in long-term expression throughout the brain has been developed. A lipid-entrapped, polycation-condensed DNA (LPD) system has been developed for brain gene delivery, using an adeno-associated vial. (“AAV”) vector in which the transcription unit is flanked by the 145 bp inverted terminal repeats (ITR) of the adeno-associated virus. This AAV plasmid is more effective than a non-ITR containing plasmid in vivo. The results show that the LPD-AAV plasmid complexes efficiently transduce neurons and that gene expression can persist for over 10 months in the brain. Furthermore, the intraventricular delivery method with systemic hyperosmolality results in global gene delivery. The examples show that expression of the human aspartoacyclase (“ASPA”) gene in children with this metabolic disorder can be obtained over a period of many months to a year, with functional activity.
Inventors
- 👤 Paola Leone
- 👤 Matthew J. During
- 👤 Frank L. Sorgi
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 11:03
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/63; C12N15/79; C12N15/85; C12N15/86; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/54; A61K47/543; A61K47/544; A61K48/00; A61K48/0008; A61K48/0025; A61K48/0041; A61K9/00; A61K9/0012; A61K9/0085; A61K9/10; A61K9/127; A61K9/1271; A61K9/1272; C12N15/87; C12N15/88; C12N9/00; C12N9/88; C12N2750/00; C12N2750/00011; C12N2750/14011; C12N2750/14111; C12N2750/14141; C12N2750/14143
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
89 words
A method for increasing gene expression in cells of the central nervous system comprising administering at or adjacent to cells of the central nervous system tissue, cation lipid associated polycation-condensed nucleic acid, wherein the cation lipid associated polycation-condensed nucleic acid comprises a cationic lipid, a polycation, and a nucleic acid encoding a protein associated with a genetic disorder, wherein the cation lipid associated polycation condensed nucleic acid enhances gene expression in the cells of the central nervous system, wherein the nucleic acid does not include an AAV coding sequence.
Claim 2
Independent Claim
89 words
A method for increasing gene expression in cells of the central nervous system comprising administering at or adjacent to cells of the central nervous system tissue, cation lipid associated polycation-condensed nucleic acid, wherein the cation lipid associated polycation-condensed nucleic acid comprises a cationic lipid, a polycation, and a nucleic acid encoding a protein associated with a genetic disorder, wherein the cation lipid associated polycation condensed nucleic acid enhances gene expression in the cells of the central nervous system, wherein the nucleic acid does not include an AAV coding sequence.
Claim 3
Dependent Claim
17 words
The method of claim 1 wherein the cation lipid associated polycation condensed nucleic acid comprises dioleoyl phosphatidylethanolamine.
Claim 4
Dependent Claim
12 words
The method of claim 2 wherein the cationic lipid is 3b-[N-(N′,N′dimethylaminoethane) carbamoyl]cholesterol.
Claim 5
Dependent Claim
19 words
The method of claim 1 wherein the polycations are selected from the group consisting of polylysine and protamine sulfate.
Claim 6
Dependent Claim
33 words
The method of claim 1 wherein the nucleic acid comprises an early cytomegalo virus promoter, a polynucleotide sequence coding for a protein associated wit a neurogenic disorder, and an SV40 poly A signal.
Claim 7
Dependent Claim
16 words
The method of claim 5 wherein the polynucleotide sequence comprises a nucleic acid sequence encoding ASPA.
Claim 8
Dependent Claim
14 words
The method of claim 1 wherein the central nervous system tissue is brain tissue.
Claim 9
Dependent Claim
16 words
The method of claim 7 wherein the cation lipid associated polycation-condensed nucleic acid is administered intracerebrally.
Claim 10
Dependent Claim
16 words
The method of claim 4 wherein the lipid-entrapped polycation-condensed nucleic acid is administered intraparenchymally or intraventricularly.
Claim 11
Dependent Claim
78 words
A composition for increasing gene expression in cells of the central nervous system comprising cation lipid associated polycation-condensed nucleic acid, wherein the cation lipid associated polycation condensed nucleic acid comprises a cationic lipid, a polycation, and a nucleic acid encoding a protein associated with a neurogenetic disorder, wherein the cation lipid associated polycation condensed nucleic acid enhances gene expression in the cells of the central nervous system, wherein the nucleic acid does not include an AAV coding sequence.
Claim 12
Dependent Claim
78 words
A composition for increasing gene expression in cells of the central nervous system comprising cation lipid associated polycation-condensed nucleic acid, wherein the cation lipid associated polycation condensed nucleic acid comprises a cationic lipid, a polycation, and a nucleic acid encoding a protein associated with a neurogenetic disorder, wherein the cation lipid associated polycation condensed nucleic acid enhances gene expression in the cells of the central nervous system, wherein the nucleic acid does not include an AAV coding sequence.
Claim 13
Dependent Claim
19 words
The composition of claim 10 wherein the polycations are selected from the group consisting of polylysine and protamine sulfate.
Claim 14
Dependent Claim
17 words
The composition of claim 10 wherein the cation lipid associated polycation condensed nucleic acid comprise dioleoyl phosphatidylethanolamine.
Claim 15
Dependent Claim
14 words
The composition of claim 12 wherein the cationic lipid is 3b- {N-(N′,N′dimethylaminoethane) carbamoyl} cholesterol.
Claim 16
Dependent Claim
22 words
The composition of claim 10 wherein the nucleic acid to be delivered comprises adeno-associated virus inverted terminal repeats flanking an expression sequence.
Claim 17
Dependent Claim
33 words
The composition of claim 10 wherein the nucleic acid comprises an early cytomegalo virus promoter, a polynucleotide sequence coding for a protein associated wit a neurogenic disorder, and an SV40 poly A signal.
Claim 18
Dependent Claim
16 words
The composition of claim 15 wherein the polynucleotide sequence comprises a nucleic acid sequence encoding ASPA.
Claim 19
Dependent Claim
16 words
The composition of claim 10 wherein the nucleic acid comprises a nucleic acid sequence encoding ASPA.
Claim 20
Dependent Claim
56 words
The method of claim 1 wherein the administration of the cation lipid associated polycation-condensed nucleic acid at or adjacent to cells of the central nervous system tissue further comprises administering before or simultaneous with the delivery of nucleic acid to the central nervous system tissue a compound which causes hypersmolarity in the central nervous system tissue.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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