University of California

C Anthony Hunt

Peter J Kushner

Paul Webb

Renee Williard

Gabriella Lopez

Marvin R Garovoy

Carol Lim

Hiroaki Yanagisawa

Martin A Apple

Sarah B Noonberg

Demetrios P Papahadjopoulous

The present invention provides novel assay methods for identifying compounds that may have both estrogen agonist and antagonist properties. In particular, the assay use cells comprising promoters having an AP1 site linked to a reporter gene. Compounds capable of inducing or blocking expression of the reporter gene can thus be identified. The compounds may be further tested for the ability to modulate the standard estrogen response, as well.

Methods for screening compounds for estrogenic activity

The invention is directed to a newly discovered class of polynucleotide decoys that is capable of competitively inhibiting the binding of transcription factors to the X-box sequence. This binding is necessary for the expression of MHC-II genes. The invention is also directed to methods of preparing these polynucleotide decoys, and methods of use thereof. In particular, we have identified a class of polynucleotide decoys that mimic the X-Box of MHC-II and competitively bind the MHC-II transcription factor RF-X, resulting in the modulation of MHC-II antigen expression. Thus, the invention can be used to inhibit the expression of HLA molecules on the surface of donor cells or organs, in order to render them invisible to the host's immune system, or in methods of treating an individual with an autoimmune disease characterized by dysfunctional expression of an MHC class II antigen. Further, because of the role of RF-X in the expression of several viral proteins, the polynucleotide decoys of the invention can be used in methods of treating an individual infected with hepatitis B virus, or cytomegalovirus.

Polynucleotide decoys that inhibit MHC-II expression and uses thereof

Compositions comprising inhibitors of estrogen response

The present invention encompasses improved methods and materials for the delivering of antisense, triplex, and/or ribozyme oligonucleotides intracellularly, and RNA polymerase III-based constructs termed 'oligonucleotide generators' to accomplish the delivery of oligonucleotides. Also encompassed by the present invention are methods for screening oligonucleotide sequences that are candidates for triplex formation.

In vivo oligonucleotide generator, and methods of testing the binding

Functional oxygen transport systems (OTS) have been devised which may serve as temporary blood substitutes in the circulatory system. The OTS comprises pure crystalline hemoglobin dissolved in an aqueous solution and encapsulated within a complex lipid and carbohydrate modified lipid phase. The hemoglobin encapsulated inner aqueous phase and the encapsulating lipid phase are dispensed in an outer isotonic aqueous phase to form a suspension of the multiple water-in-oil-in water emulsion type. The emulsion is suitable to transfusion into the circulatory system to assist in oxygen transport. The carbohydrate modified lipids are included in the lipid phase to 'mask' the OTS from the tissue binding and take up by the reticuloendothelial system. The OTS are also suitable for use as calibrating fluids in gas analysis apparatus.

Lipid-saccharide reaction products

Liposomes of uniform size are produced by forming liposomes in relatively random sizes, and extruding the liposomes under pressure through a uniform-pore-size membrane to force at least some of the liposomes into smaller sizes. Extrusion may be repeated to increase uniformity of the liposomes. The liposomes may contain an encapsulated drug.

Method for producing liposomes in selected size range

Functional oxygen transport system

A new group of compounds having an enhanced ability to inhibit nucleic acid functions have been prepared. These drugs are bis-anthracyclines wherein two anthracycline molecules are linked through their C-13 carbon atoms by amino and/or hydroxy-dicarboxylic acids and their derivatives to form the bis-compounds. Such bis-anthracyclines may be even more effectively delivered to selected sites in a mammalian organism by incorporating the same within uniformly sized liposomes.

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San Francisco, CA, United States of America

C Anthony Hunt