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-11428688-B2
Publication Date
2022-08-30
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 a magnetic multi-particle protein corona/Proteograph proteomics platform for high-throughput protein identification and protein-profiling. A particle panel disposed in one or more wells or tubes is incubated with a sample to form a plurality of distinct biomolecule coronas corresponding to distinct particle types, and the distinct particle types reproducibly generate distinct biomolecule coronas with varied physicochemical properties.
After incubation, the particle panel is magnetically isolated from unbound protein in the sample to enrich proteins in the plurality of distinct biomolecule coronas. The enriched proteins are then assayed to identify the proteins associated with the distinct coronas, and the assaying is capable of identifying from 1000 to 10,000 protein groups, providing large protein-group coverage and dynamic-range performance.
The particle panel includes an iron oxide core with a coating selected from poly(N-(3-(dimethylamino)propyl) methacrylamide) (PDMAPMA), poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), and hexane diamine. Different particle types in the panel form distinct biomolecule coronas, and the resulting protein profiles are used to associate disease or biological state, including machine-learning classifier association described in the document.
Claims Coverage
The independent claim covers a method with three core inventive features and specifies a multi-type particle panel, magnetic isolation, and assaying capable of identifying 1000 to 10,000 protein groups, with specified iron-oxide-core coatings.
Distinct biomolecule coronas from a multi-type particle panel
Incubating a particle panel disposed in one or more wells or tubes with the sample to form a plurality of distinct biomolecule coronas corresponding to distinct particle types of the particle panel.
Magnetic isolation to enrich corona-bound proteins
Magnetically isolating the particle panel from unbound protein in the sample to enrich proteins in the plurality of distinct biomolecule coronas.
Assaying to identify 1000 to 10,000 protein groups with iron-oxide-core coatings
Assaying the plurality of distinct biomolecule coronas to identify the enriched proteins, wherein the assaying is capable of identifying from 1000 to 10,000 protein groups, and wherein the particle panel comprises a particle type having an iron oxide core with a coating selected from poly(N-(3-(dimethylamino)propyl) methacrylamide) (PDMAPMA), poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), and hexane diamine.
The independent claim establishes the core inventive approach as forming multiple distinct biomolecule coronas using a multi-type particle panel, magnetically isolating the panel to enrich corona-bound proteins, and assaying the coronas for protein-group identification at 1000 to 10,000 protein groups, with specified iron-oxide-core coatings.
Stated Advantages
High-throughput protein identification and protein profiling.
Large protein-group coverage, capable of identifying from 1000 to 10,000 protein groups.
Dynamic-range performance.
Automation-compatible batch processing.
Reproducibility performance using QNCV of variation thresholds.
Association with disease or biological state, including early cancer detection signals and cancer differentiation accuracy described in examples.
Documented Applications
Corona-analysis platform application using cancer-related plasma/serum studies and patient cohort descriptions for CRC and NSCLC, using liposome or SPION panels to achieve separation/classification signals.
Biomarker discovery and panel optimization/validation using large protein databases and comparisons involving CV and spike recovery, including CRP recovery, in described studies.
Associating disease or biological state using protein profiles generated from distinct biomolecule coronas.
Early cancer detection signals described as up to ~8 years prior, with cancer differentiation accuracy described in examples.
Biomarker discovery described in the document, including reference to FDA-cleared/approved biomarkers.
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