Anti-gene Development Group

Gene Tools, LLC

Antivirals Inc.

Avi Biopharma, Inc.

Other

University of Nebraska

Anti-gene Deveopment Group

Neu-gene Development Group

James E Summerton

Dwight D Weller

Eugene P Stirchak

Patrick L Iversen

Randall E Brand

James Patrick Summerton

Paul Anton Morcos

John M Wages, Jr

Improved compositions have been developed which are selectively sequestered in acidic areas of tumors. When the compositions contain a radioisotope effective to report the presence of the composition, the compositions are useful for detecting tumors. When the compositions contain radioisotopes effective to kill cells, the compositions are useful for treating tumors. Methods for detecting and treating tumors with such compositions are also disclosed.

Compositions and methods for detecting and treating tumors containing acidic areas

Embedder compositions effective for detecting or killing cells in acidic areas of tumors are described. Each composition includes an embedder peptide which at pH 7.2 and above is poly-anionic and so repels from cells in normal tissues, but at lower pH in hypoxic areas of tumors the embedder peptide converts to a non-ionic lipophilic form effective to embed into membranes of cells. Each composition also includes a cargo component which cannot be pulled across cell membranes by the embedder peptide and which is effective for detecting or killing cells in whose membranes the embedder peptide has embedded.

Embedder compositions and methods for detecting and killing cells in acidic areas of tumors

Improved transporter compositions effective for detecting or killing cells in acidic areas of tumors are described. Each composition includes a transporter peptide which at pH 7.2 and above is poly-anionic and so repels from cells in normal tissues, but at lower pH in hypoxic areas of tumors the transporter peptide converts to a non-ionic lipophilic form which transports across membranes of cells. Each composition also includes a cargo component which can be pulled across cell membranes by the transporter peptide and which is effective for detecting or killing cells into which the transporter composition has entered.

Transporter compositions and methods for detecting and killing cells in acidic areas of tumors

Weak-base amphiphilic delivery peptide compositions are described for use in delivering large polar substances (cargo) into the cytosol of animal cells via an indirect endocytosis-mediated delivery process. The delivery peptides, which are predominantly non-ionic at neutral pH, bind but do not permeabilize cell membranes. After endocytosis of both delivery peptides and cargo, acidification of the endosome converts the delivery peptides to their polycationic form, whereupon they permeabilize the endosomal membrane and allow co-endocytosed cargo to pass from the endosome to the cytosol of the cell.

Peptide composition and method for delivering substances into the cytosol of cells

The invention relates to a composition, solution, and method for delivering desired substances into the cytosol of living eucaryotic cells. The composition includes a poly(ethylene glycol) component having a designated molecular weight in the range between about 300 and about 900 daltons, and a carbohydrate component which is membrane impermeable and water soluble. The osmotic delivery solution delivers reporter-tagged molecules and complexes, drugs, antisense and antigene oligos, RNAs, DNAs, peptides, proteins, carbohydrates, and the like into cultured cells using an improved osmotic delivery method. The method may also be used for extracorporal therapy. In a particularly preferred embodiment of extracorporal therapy, the desired substance delivered into the cytosol of the cells is a Morpholino antisense oligo.

Osmotic delivery composition, solution, and method

A method and comjugate for treating H. pylori infection in a subject are disclosed. The conjugate is composed of (a) a nuclease-resistant antisense oligomer effective to inhibit H. pylori infection in the subject by base-specific Watson-Crick binding to an H. pylori mRNA transcript, and (b) a transport moiety conjugated to the oligomer. The transport moiety is effective to facilitate uptake of the conjugate from the environment of the stomach into the cytoplasm of H. pylori cells by active transport or by pH-gradient transport across of the cell membrane of H. pylori. The conjugate is administered by oral route, preferably in a swellable polymer bolus designed to release the conjugate in sustained release.

Method and conjugate for treating H. pylori infection

The invention relates to compositions and methods for rapidly detecting or isolating a target nucleic acid sequence in a polynucleotide-containing sample. The sample is exposed to a rapid pairing reagent, which contains a rapid capture component, effective to rapidly and non-selectively bind polynucleotides, and a target specific probe, effective to selectively bind the target nucleic acid sequence. Selectively disrupting the binding between the capture component and polynucleotides leaves only target sequence bound to the rapid pairing reagent.

Reagent and method for isolation and detection of selected nucleic acid

Polymeric compositions effective for delivering compounds in living organisms are described. The compositions include polypeptides which exhibit solubility in both hydrophilic and lipophilic environments by undergoing a reversible pH-dependent transition from a low-pH, lipophilic form to a high-pH, hydrophilic form.

Polymer composition for delivering substances in living organisms

A method of generating a compound capable of interacting specifically with a selected macromolecular ligand is disclosed. The method involves contacting the ligand with a combinatorial library of oligomers composed of morpholino subunits with a variety of nucleobase and non-nucleobase side chains. Oligomer molecules that bind specifically to the receptor are isolated and their sequence of base moieties is determined. Also disclosed is a combinatorial library of oligomers useful in the method and novel morpholino-subunit polymer compositions.

Morpholino-subunit combinatorial library and method

The present invention describes an assay system wherein target polynucleotide molecules are captured on a support by base-specific binding to support-bound polymers, which are themselves substantially uncharged, and the target polynucleotides can be detected on the basis of their backbone charge. The assay system may also include polycationic reporter molecules which are designed to bind to the fully charged analyte backbone, but not the uncharged (or substantially uncharged) polymer backbone. In one embodiment, the reporter molecules are composed of a polycationic moiety or tail designed to bind electrostatically to a fully charged polynucleotide, under conditions where the reporter does not bind to the less charged or uncharged binding polymer carried on the diagnostic reagent.

Polynucleotide reagent containing chiral subunits and methods of use

A composition of polymer molecules effective to bind, with substantially uniform binding affinity, to a single-stranded polynucleotide containing a target sequence of bases. The polymer molecules are composed of a sequence of base-pairing moieties effective to hydrogen bond to corresponding, complementary bases in the target sequence, under selected binding conditions, and a predominantly uncharged, achiral backbone supporting the base-pairing moieties at positions and in orientations which allow hydrogen bonding between the pairing moieties of the polymer and the corresponding complementary bases in the target sequence. The composition has diagnostic uses, in a solid-support assay system, and therapeutic uses involving inhibition or inactivation of target polynucleotides.

Uncharged polynucleotide-binding polymers

The present invention describes a polymer composition effective to bind, in a sequence-specific manner to a target sequence of a duplex polynucleotide, at least two different-oriented Watson/Crick base-pairs at selected positions in the target sequence. The composition includes an uncharged backbone with 5- or 6-membered cyclic backbone structures and selected bases attached to the backbone structures effective to hydrogen bond specifically with different oriented base-pairs in the target sequence. Also disclosed are subunits useful for the construction of the polymer composition. The present invention further includes methods for (i) coupling a first free or polymer-terminal subunit, and (ii) isolating, from a liquid sample, a target duplex nucleic acid fragment having a selected sequence of base-pairs.

Sequence-specific binding polymers for duplex nucleic acids

Alpha-morpholino subunits and polymer compositions composed of alpha-morpholino subunits are disclosed. These subunits can be linked together by uncharged linkages, one to three atoms in length, joining the morpholino nitrogen of one subunit to the 5' exocyclic carbon of an adjacent subunit. Each subunit contains a purine or pyrimidine base-pairing moiety effective to bind by hydrogen bonding to a specific base or base-pair in a target polynucleotide. The polymers of the instant invention can be used in place of standard RNA or DNA oligomers. For example, the target-specific polymers of the invention can be used in a variety of diagnostic assays for detection of RNA or DNA having a given target sequence. Further, the polymers of the invention also have potential use as therapeutic agents.

Alpha-morpholino ribonucleoside derivatives and polymers thereof

Alpha-morpholino subunits and polymer compositions composed of alpha-morpholino subunits are disclosed. These subunits can be linked together by uncharged linkages, one to three atoms in length, joining the morpholino nitrogen of one subunit to the 5' exocyclic carbon of an adjacent subunit. Each subunit contains a purine or pyrimidine base-pairing moiety effective to bind by hydrogen bonding to a specific base or base-pair in a target polynucleotide. The polymers of the present invention can be used in place of standard RNA or DNA oligomers for a number of standard laboratory procedures, for example, as probes in solid-phase systems and nucleic acid hybridization analyses. Further, the polymers of the present invention have potential use as therapeutic agents in anti-sense-type technologies.

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Corvallis, OR, United States of America

James E Summerton