Abstract: The invention discloses that methylated nucleic acids, particularly methylated oligonucleotides, and more particularly methylated oligonucleotides bearing a methylated cytosine of a CpG dinucleotide motif can be made immunostimulatory in vivo, by encapsulation of the nucleic acid in a lipid particle. It is further disclosed that encapsulated methylated nucleic acids that are ordinarily not immunostimulatory in vivo are as effective or even more effective than their encapsulated unmethylated counterparts. Also disclosed are methods for activating and/or expanding dendritic cell populations in response to antigenic stimulation using the compositions and methods disclosed herein.

Abstract: The invention is based on the discovery that vaccines against pathogens, exemplified herein by hepatitis B, can be formulated to enhance stimulation of Th1 type humoral and cellular immune responses by combining a lipid particle with an encapsulated immunostimulatory oligonucleotide (LNA). The LNA is further associated with an antigen from the pathogen. The vaccines may also use two or more different epitopes from the same antigen, or different antigens from the pathogen. Such vaccines are particularly effective in enhancing a Th1 type humoral response when the antigen is coupled to the lipid nucleic acid particle and when the nucleic acid particle has phosphorothioate (PS) backbone. An enhanced humoral response is demonstrated, for example, by a strong early peak of IFN-gamma production observed within hours of vaccination followed by second stronger peak of IFN-gamma production observed several days later, correlated with antibody isotype switching.

Abstract: Methods for the preparation of a lipid-nucleic acid composition are provided. According to the methods, a mixture of lipids containing a protonatable or deprotonatable lipid, for example an amino lipid and a lipid such as a PEG- or Polyamide oligomer-modified lipid is combined with a buffered aqueous solution of a charged therapeutic agent, for example polyanionic nucleic acids, to produce particles in which the therapeutic agent is encapsulated in a lipid vesicle. Surface charges on the lipid particles are at least partially neutralized to provide surface-neutralized lipid-encapsulated compositions of the therapeutic agents. The method permits the preparation of compositions with high ratios of therapeutic agent to lipid and with encapsulation efficiencies in excess of 50%.

Abstract: Lipid-nucleic acid particles can provide therapeutic benefits, even when the nucleic acid is not complementary to coding sequences in target cells. It has been found that lipid-nucleic acid particles, including those containing non-sequence specific oligodeoxynucleotides, can be used to stimulate cytokine secretion, thus enhancing the overall immune response of a treated mammal. Further, immune response to specific target antigens can be induced by administration of a antigenic molecule in association with lipid particles containing non-sequence specific oligodeoxynucleotides. The nucleic acid which is included in the lipid-nucleic acid particle can be a phosphodiester (i.e.

Abstract: The present invention relates to compositions and methods for delivering nucleic acid catalysts e.g., vascular endothelial growth factor receptor (VEGF-R-1) ribozyme, into a biological system.

Abstract: This invention relates to improved liposomal camptothecin compositions and methods of manufacturing and using such compositions for treating neoplasia and for inhibiting angiogenesis.

Abstract: This invention relates to liposomal antineoplastic agents (e.g., camptothecin) compositions and methods of using such compositions for treating neoplasia and for inhibiting angiogenesis. The compositions and methods are useful for modulating the plasma circulation half-life of an active agent.

Abstract: Lipid-therapeutic agent particles are prepared containing a charged therapeutic agent encapsulated in lipid portion containing at least two lipid components including a protonatable or deprotonatable lipid such as an amino lipid and a lipid that prevents particle aggregation during lipid-therapeutic agent particle formation such as a PEG-modified or polyamide oligomer-modified lipid. Other lipid components may also be present and these include a neutral lipid such as DSPC, POPC, DOPE or SM, and a sterol such as Chol. The therapeutic agent is encapsulated by combining a mixture of the lipids with a buffered aqueous solution of a charged therapeutic agent to form an intermediate mixture containing lipid-encapsulated therapeutic agent particles, and changing the pH of the intermediate mixture to neutralize at least some surface charges on the particles. The method permits high ratios of therapeutic agent to lipid and encapsulation efficiencies in excess of 50%.