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Home Gene Therapy Method-for-the-liposomal-delivery-of-nucleic-acids

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 Method for the liposomal delivery of nucleic acids

Details
Inventors: Thierry, Alain;
Assignee: The United States of America as represented by the Department of Health (Washington, DC)
Primary Examiner: Page; Thurman K.
Assistant Examiner:
Attorney, Agent or Firm: Morgan & Finnegan, L.L.P.

The present invention is directed to a liposomal preparation which is based on specific lipid components. The liposomal compounds are also combined with nucleic acids, forming nucleic acid-liposomal compounds. These compounds are useful in drug delivery, where specific therapeutic nucleic acids are used in the liposomes. The specific lipid components of the present invention provide a highly efficient and stable delivery system for nucleic acids. Consequently, the liposomal preparations are suitable for use in gene therapy.

DETAILED DESCRIPTION The present invention relates to a nucleic acid-liposome preparation, useful in delivery of nucleic acid-based materials to cells.
The present invention further relates to a method of preparing the nucleic acid-liposome preparations.
In addition, the present invention relates to the administration of the nucleic acid-liposome preparations to cells.
The invention further relates to administration of the nucleic acid liposome preparations to patients as a therapeutic agent.
The liposome compositions of the present invention provide highly efficient delivery of nucleic acids to cells.
Liposome vesicles are prepared from a mixture of a cationic lipopolyamine and a neutral lipid.
Nucleic acids are associated with the liposomes in two ways: (1)complex formation between the cationic liposome vesicle and negatively charged nucleic acid or (2) partial encapsulation and partial complex formation in and with the cationic liposome vesicle.
A preferred embodiment of the present invention uses a spermine-5-carboxy-glycinedioctadecylamide (referred to herein as "DOGS") as the cationic lipopolyamine and dioleylphosphatidyl ethanolamine (referred to herein as "DOPE") as the neutral lipid.
Another embodiment of the present invention is directed to a combination of a DOGS/DOPE liposome preparation (referred to herein as "DLS-liposomes") anchored through hydrophobic interactions with an adenovirus particle.
Since adenoviruses enter cells via receptor-mediated endocytosis, the combination of adenovirus particles and the DLS-liposomes produces an enhanced transduction efficiency.
One embodiment of the present invention is directed to a liposomal preparation which is based on a composition of nucleic acids or analogues and DOGS containing liposomes.
The liposomes of the present invention efficaciously deliver nucleic acids into the cytoplasmic compartment of human cells.
Use of such liposomal vehicles, and use of plasmid DNA as a carrier of a gene of interest, make possible high expression of such gene in cells or in a patient



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