IP Library Granted Patent US 12,359,220
Granted Patent B2
US 12,359,220 · App. 16/962,509 · Granted Jul 15, 2025

Guided magnetic nanostructures for targeted and high-throughput intracellular delivery

Inventors: Paul S. Weiss (Los Angeles, CA); Hsian-Rong Tseng (Los Angeles, CA); Xiaobin Xu (Los Angeles, CA); Natcha Wattanatorn (Los Angeles, CA); Qing Yang (Los Angeles, CA); Steven J. Jonas (Hawthorne, CA)
Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
C12N15/87G01N33/54326C12N2310/141
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Quick Facts
Patent No.
US 12,359,220
App. No.
16/962,509
Granted
Jul 15, 2025
Kind
B2
Abstract

A method of transporting biomolecular cargo intracellularly into cells includes the operations of providing magnetic nanostructures (e.g., nanospears, nanostars, nanorods, and other nanometer-sized structures) carrying the biomolecular cargo thereon and applying an external magnetic field to move the magnetic nanostructures into physical contact with at least some of the cells (or the cells into the magnetic nanostructures). The magnetic nanostructures move into physical contact with a single cell, a subset of cells, or all cells. The external magnetic field may be applied by a moving permanent magnet although an electromagnetic may also be used. The biomolecular cargo may include a molecule, a plurality of molecules, or higher order biological constructs. For example, the biological construct may include DNA plasmids, small interfering RNA, proteins, or targeted nuclease gene-editing cargo such as zinc-finger nucleases, transcription activator-like effector nucleases, Cas9 protein, Cas9 mRNA, and associated guide RNA sequences.

Claims (14)

1. A method of transporting biomolecular cargo intracellularly into a plurality of cells comprising:

providing a microfluidic channel;

providing a plurality of magnetic nanostructures carrying the biomolecular cargo thereon within the microfluidic channel, wherein the plurality of magnetic nanostructures have at least one pointed end or tip;

flowing a fluid containing the plurality of magnetic nanostructures within the microfluidic channel;

applying an external magnetic field to maintain the plurality of magnetic nanostructures in a substantially stationary state along a width of the microfluidic channel and orients the plurality of magnetic nanostructures to place the at least one pointed end or tip of the plurality of magnetic nanostructures opposite to a direction of flow within the microfluidic channel; and

flowing the plurality of cells within the microfluidic channel to physically contact the at least one pointed end or tip of the plurality of magnetic nanostructures.

2. The method of claim 1 , wherein the plurality of magnetic nanostructures comprises a first type of magnetic nanostructure carrying a first biomolecular cargo thereon and a second type of magnetic nanostructure carrying a second biomolecular cargo thereon.

3. The method of claim 1 , wherein the plurality of magnetic nanostructures are biodegradable by the plurality of cells.

4. The method of claim 1 , wherein the plurality of magnetic nanostructures comprise a silicon base, followed by a nickel layer and a gold layer, followed by a layer of polyethyleneimine (PEI).

5. The method of claim 1 , wherein the biomolecular cargo comprises one or more molecules.

6. The method of claim 1 , wherein the biomolecular cargo comprises DNA-containing plasmids.

7. The method of claim 1 , wherein the biomolecular cargo comprises targeted nucleases for gene editing and their associated guide nucleic acid sequences.

8. The method of claim 1 , wherein the plurality of magnetic nanostructures comprise silicon coated with a magnetically susceptible metal followed by a noble metal or metal oxide layer.

9. The method of claim 8 , wherein the biomolecular cargo is electrostatically and/or covalently attached or tethered to a deposited surface layer formed over the noble metal or metal oxide layer.

Assignments (3)
CONFIRMATORY LICENSE Recorded May 23, 2023
From: UNIVERSITY OF CALIFORNIA LOS ANGELES
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 063724/0680 →
CONFIRMATORY LICENSE Recorded Jan 5, 2021
From: UNIVERSITY OF CALIFORNIA, LOS ANGELES
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 054903/0110 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 16, 2020
From: WEISS, PAUL S.; TSENG, HSIAN-RONG; XU, XIAOBIN; WATTANATORN, NATCHA; YANG, QING; JONAS, STEVEN J.
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 053222/0746 →
Continuity (2)
Provisional Application 62623449 · Jan 29, 2018
Related Publication 20200347409A1 · Nov 5, 2020
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