University of Pittsburgh

Other

Targeted Genetics Corporation

Frank L Sorgi

Leaf Huang

Xiang Gao

Matthew J During

Ralph Wilfred Paul

Aaron Garth Loomis

Paola Leone

David L Sloane

Novel stable, concentrated, biologically active and ready-to-use lipid-comprising drug delivery complexes and methods for their production are described. The biological activity of the complexes produced are comparable to the formulations prepared according to the prior art admixture method and upon purification, the complexes produced by the method of this invention are 50 to 500 fold more concentrated than the complexes formed by admixture. The method described herein provides for the large scale production of lipid-comprising drug delivery systems useful for gene therapy and other applications.

Stable lipid-comprising drug delivery complexes and methods for their production

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. (&ldquo;AAV&rdquo;) 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 (&ldquo;ASPA&rdquo;) gene in children with this metabolic disorder can be obtained over a period of many months to a year, with functional activity.

Delivery system for gene therapy to the brain

Stable lipid-comprising drug delivery complexes and methods for their

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Sonoma, CA, United States of America

Frank L Sorgi