Compositions, methods and systems for protein corona analysis and uses thereof
Inventors
XIA, Hongwei • HESTERBERG, Lyndal • Figa, Michael • Zhao, Xiaoyan • Troiano, Gregory • Manning, William • Blume, John • Farokhzad, Omid • McLean, Matthew • Stolarczyk, Craig • KO, Marwin • Platt, Theodore
Assignees
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Publication Number
US-12222349-B2
Publication Date
2025-02-11
Expiration Date
Abstract
Compositions, methods, and systems for analyzing the protein corona are described herein, as well as its application in the discovery of advanced diagnostic tools as well as therapeutic targets.
Core Innovation
The invention relates to identifying proteins in a biological sample by incubating a plurality of magnetic particles configured to bind proteins, forming protein coronas. The magnetic particles comprise a polymer bearing ammonium functional groups and have a positive zeta potential in a specified range, and the bound corona proteins are magnetically isolated from the biological sample while unbound protein fractions are separated.
The associated proteins are processed for proteomic data generation by reducing the proteins and digesting the proteins, followed by mass spectrometry analysis to quantify proteins and protein groups. The resulting proteomic data are used to build and apply classifiers and to link resulting protein profiles to a subject biological state.
The document also describes panel design and selection for protein-corona formation, including permutations in the number of particle types and physicochemical distinctions such as size, PDI, surface charge, morphology, chemical functional groups, surface chemistry, and porosity. Particle materials described include polymers, lipids, metals, and superparamagnetic iron oxide nanoparticles.
Claims Coverage
The independent claims cover kits for identifying proteins in a biological sample using magnetic particles with a positively charged polymer, together with a reducing agent and an enzymatic agent. Across the independent claims, there are 3 main inventive claim groupings distinguished by the ammonium functionality and polymer composition while maintaining the same core kit structure and zeta-potential constraint.
Magnetic particles with positively charged ammonium-functional polymer for protein corona binding
A plurality of magnetic particles configured to bind a plurality of proteins in the biological sample when the plurality of magnetic particles is incubated with the biological sample, wherein the plurality of magnetic particles comprise a polymer, wherein the polymer comprises an ammonium functional group, wherein the plurality of magnetic particles comprise a positive zeta potential, and wherein the positive zeta potential ranges from 10 mV to 60 mV.
Reducing agent to reduce proteins
A reducing agent configured to reduce the plurality of proteins.
Enzymatic agent to digest proteins
An enzymatic agent configured to digest the plurality of proteins.
Ammonium functionality defined as tertiary ammonium
The polymer comprises an ammonium functional group, wherein the ammonium functional group comprises a tertiary ammonium.
Ammonium functionality defined as quaternary ammonium
The polymer comprises an ammonium functional group, wherein the ammonium functional group comprises a quaternary ammonium.
Polymer comprised of divinylbenzene
The polymer comprises divinylbenzene.
Across the independent claims, the kits rely on magnetic particles with ammonium-functional polymers having a positive zeta potential ranging from 10 mV to 60 mV, together with a reducing agent and an enzymatic agent to reduce and digest the proteins. Additional independent-claim-level variation specifies the ammonium type and/or the polymer composition.
Stated Advantages
Documented Applications
No documented applications found
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