Granted Patent B2

US 12,612,656 · App. 18/058,000 · Granted Apr 28, 2026

Inventors: Julia Robinson (East Palo Alto, CA); Tural Aksel (Redwood City, CA)

Assignee: Nautilus Subsidiary, Inc.

C12Q1/6834C12Q1/6816C12Q1/6837C12Q2525/205C12Q2525/30

Abstract

Claims (21)

1 . A method comprising

(a) forming a reaction mixture comprising:

(i) a plurality of proteins, wherein individual proteins of the plurality of proteins each comprise a plurality of first reactive moieties, wherein the plurality of proteins comprises at least 100 different primary protein structures, and

(ii) a plurality of particles, wherein individual particles of the plurality of particles each comprise a structured nucleic acid particle and a second reactive moiety, wherein the second reactive moiety of the particles is reactive with the first reactive moieties of the proteins, and wherein each of the particles is immobilized on a solid support;

(b) reacting a first reactive moiety of a protein in the reaction mixture with a second reactive moiety of a particle in the reaction mixture to attach the protein to the particle via a bond formed between the first reactive moiety of the protein and the second reactive moiety of the particle, wherein the reacting yields no more than one protein attached to the particle, and wherein immobilization of the particles inhibits more than one of the particles in the reaction mixture from simultaneously contacting the protein, thereby forming an immobilized particle-protein conjugate on the solid support; and

(c) detaching the immobilized particle-protein conjugate from the solid support in solution-phase, thereby producing a solution-phase particle-protein conjugate.

2 . The method of claim 1 , wherein the structured nucleic acid particles comprise nucleic acid origami.

3 . The method of claim 1 , wherein the individual particles each comprise a nucleic acid linker attaching the individual particle to the second reactive moiety.

4 . The method of claim 1 , wherein each of the individual particles comprises a single second reactive moiety.

5 . The method of claim 1 , further comprising quenching reactivity of the second reactive moiety or the first reactive moiety after step (b).

6 . The method of claim 5 , wherein the quenching comprises attaching a ligand to the second reactive moiety.

7 . The method of claim 6 , further comprising separating particles from the particle-protein conjugate via binding of a receptor to the ligand.

8 . The method of claim 1 , further comprising (d) binding a probe to the protein of the particle-protein conjugate.

9 . The method of claim 8 , further comprising (e) detecting the binding of the probe to the protein of the particle-protein conjugate.

10 . The method of claim 8 , further comprising attaching the particle-protein conjugate to a solid support prior to step (d), thereby binding the probe to the protein of the particle-protein conjugate on the solid support.

11 . The method of claim 1 , further comprising, after step (c), separating the particle-protein conjugate from particles that lack an attached protein.

12 . The method of claim 11 , further comprising attaching the protein-attached particles to a second solid support, thereby forming an array of protein-attached particles.

13 . The method of claim 2 , wherein the nucleic acid origami comprises a plurality of at least 50 oligonucleotides hybridized to a scaffold nucleic acid.

14 . The method of claim 2 , wherein the nucleic acid origami comprises a staple oligonucleotide hybridized to two regions of a scaffold nucleic acid that are separated from each other in the nucleotide sequence of the scaffold nucleic acid.

15 . The method of claim 1 , wherein the plurality of proteins comprises at least 60% of the proteins encoded by a human proteome.

16 . The method of claim 1 , wherein, prior to step (a), the plurality of proteins is modified to add the first reactive moieties to the proteins.

Assignments (2)

Continuity (2)

References Cited (288)