Methods for assembling scavenging particles

Inventors

Hawthorne, Louis • Dodgson, John

Abstract

The disclosure provides, methods for preparing scavenging particles, as well as methods for attaching capture agents to the particles. The disclosure further provides compositions that bind to and inhibit the biological activity of soluble biomolecules, as well as pharmaceutical compositions thereof. The compositions may comprise a plurality of particles that specifically bind a target, such as a soluble biomolecule or a biomolecule on the surface of a pathogen, to inhibit the target (or pathogen) from interacting with other molecules or cells. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.

Core Innovation

The patent describes exosome/vesicle scavenging particle architectures that include coupled particles defining a capture environment and a protected surface region adjacent to that capture environment. A first agent is immobilized on the first region of protected surface and is configured so the first agent can bind a first molecule on the surface of an exosome. The capture environment is a volume between the surface of a first particle and a second particle, with a characteristic dimension from 30 nm to 1 µm.

The disclosed constructs further emphasize protected surface regions having physical openings and/or protected geometries, such as cups, tubes, recesses, voids, recess pores, and spaced subparticles, sized to capture exosomes by presenting exosome-surface binding agents while inhibiting unwanted cell-surface binding. The patent also describes DNA-scaffold-based particle structures that can form three-dimensional shapes with an opening.

To enable scavenging functionality, the patent expands the immobilized agent toolbox and chemistries, including DNA scaffold attachment via oligonucleotide binding pairs and surface functionalization on silica using reactive groups and linkers. The patent also describes immobilization approaches using reactive groups and linkers, including nucleic-acid hybridization, and lists example agent categories such as aptamers, antibodies and fragments, and cytokine/NF-κB/TNF-family ligands/decoys, which support binding of targeted molecules on an exosome surface.

Claims Coverage

The independent claims define three core inventive features: a coupled-particle capture environment sized from 30 nm to 1 µm, protected surface regions adjacent to the capture environment with immobilized agents binding exosome surface molecules, and selective chemistry via reactive groups that couple predetermined-functional-group agents to enable exosome binding.

Across the independent claims, the constructs rely on coupled particles forming a capture environment with a characteristic dimension from 30 nm to 1 µm, protected surface regions adjacent to that environment, and agent binding to molecules on an exosome surface. The second independent claim additionally requires two distinct immobilized agents on separate protected surface regions, while the third independent claim introduces a reactive group that selectively couples a predetermined-functional-group-bearing agent to enable exosome binding.

Stated Advantages

Documented Applications