University of Washington

Vanderbilt University

Phaserx, Inc.

Genevant Sciences Gmbh

University of Florida Research Foundation Inc

The United States Government As Represented by the Department of Veterans Affairs

Craig L Duvall

Allan Sachs Hoffman

Patrick S Stayton

Paul Hickok Johnson

Anthony Convertine

Anna S Gall

Robert W Overell

Danielle Benoit

Mary Gallagher Prieve

Charbel Diab

Priyadarsi De

Mukesh Kumar Gupta

Amber E E Paschal

Anthony J Convertine

Paul Johnson

Scott A Guelcher

Thomas A Werfel

John R Martin

Christopher E Nelson

Samantha M Sarett

Brian Connor Evans

Lawrence J Marnett

Colleen M Brophy

Benjamin George Keselowsky

Kyle Hocking

Amber E Paschal

Brenda C Crews

Jeffrey M Davidson

Jamal Lewis

Jonathan M Page

Jashim Uddin

Kristin P O'Grady

Robert Overell

Lawrence Premasiri Fernando

Lirong Yang

James Kintzing

Joshua M Shannon

Elizabeth J Adolph

Madison McGough

Jon Page

Amber Ee Paschal

Madison AP Mcgough

Provided herein are compounds and methods for gene silencing. The compound includes a RNA directly conjugated to an albumin-binding group. The method includes administering a compound comprising a RNA directly conjugated to an albumin-binding group to a subject in need thereof.

Conjugation of lipophilic albumin-binding moiety to RNA for improved carrier-free in vivo pharmacokinetics and gene silencing

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instauces, micellic assemblies provided herein are pH sensitive particles.

Micellic assemblies

The present disclosure relates to compounds comprising (i) an active agent, wherein the active agent includes a charge at a predetermined pH, (ii) a polymer, wherein the polymer includes an opposite charge than the active agent at the predetermined pH; and (iii) a polyplex comprising the peptide and the polymer electrostatically bond together at the predetermined pH. In some embodiments, the active agent is a peptide, such as a peptide comprising MAPKAP kinase II inhibitory peptide, and in some embodiments the peptide includes a cell-penetrating peptide. In further embodiments, the disclosure provides methods for treating a disease or condition by administering a composition according to the present disclosure to a subject in need thereof.

Polyplexes

A reactive oxygen species savaging emulsion; the emulsion comprising an injectable pharmaceutically acceptable composition and a polymeric poly(propylene sulfide) microsphere for targeted delivery to a site with elevated reactive oxygen species. In embodiments of the present invention, the microsphere is loaded with a biologically active agent.

Reactive oxygen species (ROS)-responsive compositions and methods thereof

Embodiments of the present disclosure include particles, methods of making particles, methods of delivering an active agent using the particle, and the like.

Polymeric particles, method for cytosolic delivery of cargo, methods of making the particles

The presently-disclosed subject matter includes nanoparticles that comprise a plurality of assembled polymers. In some embodiments the polymers comprise a first block that includes hydrophilic monomers, the first block substantially forming an outer shell of the nanoparticle, and a second block that includes cationic monomers and hydrophobic monomers, the second block substantially forming a core of the nanoparticle. In some embodiments a polynucleotide is provided that is bound to the cationic monomers of the nanoparticle. The presently-disclosed subject matter also comprises methods for using the present nanoparticles to include RNAi in a cell as well as methods for making the present nanoparticles.

Polymeric nanoparticles

Disclosed are compositions that comprise a cyclooxygenase-2-selective therapeutic and/or diagnostic agent having a therapeutic and/or diagnostic agent conjugated to a NSAID drug; and a ROS-responsive nanoparticle. Methods of making and using these compositions for drug encapsulation and delivery are also disclosed.

Fluorocoxib A loading into ROS-responsive nanoparticles

A biodegradable scaffold, a low-molecular weight thioketal, and a method of forming a biodegradable scaffold are provided. The biodegradable scaffold includes a thioketal and an isocyanate, where the thioketal is linked to the isocyanate to form the scaffold. The low-molecular weight thioketal includes 2,2-dimethoxypropane and thioglycolic acid, wherein the thioketal includes at least two hydroxyl terminal groups. The method of forming the biodegradable scaffold includes blending a thioketal with an excess isocyanate, forming a quasi-prepolymer, mixing the thioketal, the quasi-prepolymer, and a ceramic, and then adding a catalyst to form the biodegradable scaffold. The thioketal is a low-molecular weight thioketal having at least two hydroxyl terminal groups.

Poly(thioketal-urethane) scaffolds and methods of use

Described herein are copolymers, and methods of making and utilizing such copolymers. Such copolymers have at least two blocks: a first block that has at least one unit that is hydrophilic at physiologic pH, and a second block that has hydrophobic groups. This second block further has at least one unit with a group that is anionic at about physiologic pH. The described copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the copolymer is endosomolytic.

Diblock copolymers and polynucleotide complexes thereof for delivery into cells

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instances, micellic assemblies provided herein are pH sensitive particles.

The presently-disclosed subject matter includes biodegradable scaffolds. Exemplary biodegradable scaffolds comprise a plurality of polythioketal polymers, and a plurality of polyisocyanates, where at least one polyisocyanate is linked to at least one polymer to form the scaffold. Thus, certain embodiments of scaffolds comprise a cross-linked network of the polythioketal polymers and the polyisocyanates. The presently-disclosed subject matter also includes methods for treating tissue, such as skin or bone tissue, in a subject in need thereof. Treatment methods comprise contacting the tissue with an effective amount of the biodegradable scaffold. Furthermore, the presently-disclosed subject matter includes methods for making the present biodegradable scaffolds.

Growing community of inventors

Nashville, TN, United States of America

Craig L Duvall