# US 12,005,265 B2 · Compositions and methods to modulate cell activity

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- Number: US 12,005,265 B2
- Document ID: US12005265B2
- Status: Granted
- Kind: B2
- Application number: 16/986,482
- Filed: 2020-08-06
- Published: 2021-02-25
- Granted: 2024-06-11
- Earliest claimed: 2014-09-22
- Assignees: The Rockefeller University; Rensselaer Polytechnic Institute
- Applicants: The Rockefeller University; Rensselaer Polytechnic Institute
- Inventors: Sarah Stanley; Jeffrey Friedman; Jonathan S. Dordick; Jeremy Sauer
- Web page: https://patentgrep.com/patent/US12005265B2

## CPC

- A61N 2/002: {in combination with another treatment}
- A61K 38/28: Insulins
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 48/0075: {characterised by an aspect of the delivery route, e.g. oral, subcutaneous}
- A61N 2/00: Magnetotherapy
- A61N 2/004: {specially adapted for a specific therapy}
- A61N 2/06: using magnetic fields produced by permanent magnets (A61N2/12 takes precedence)
- A61N 5/025: {Warming the body, e.g. hyperthermia treatment}
- C12N 15/62: DNA sequences coding for fusion proteins
- C12N 15/86: Viral vectors
- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels}
- A61K 9/51: Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)}
- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 2319/00: Fusion polypeptide
- C12N 2710/10343: viral genome or elements thereof as genetic vector
- C12N 2800/30: Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
- G01N 2800/042: Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention provides methods and compositions for the remote control of cell function based on the use of a magnetic field to excite paramagnetic nanoparticles targeted to specific cell types. The cell type of interest expresses an ion channel wherein excitation of the paramagnetic nanoparticles results in a physical change that is transduced into a cellular response. Such cellular responses may include, for example, increases in gene expression resulting in production of one or more physiologically active proteins. The expression of such proteins can be used to treat a variety of different inherited or acquired diseases or disorders in a subject.

## Claims

### Claim 1

A method of modulating the activity of a population of cells, comprising the steps of:
(a) providing a population of recombinant cells, said cells comprising a genetic construct comprising a nucleotide sequence which encodes an iron-binding protein fused to a first polypeptide and a nucleotide sequence which encodes a TRPV1Mutant ion channel fused to a second polypeptide, wherein the first polypeptide is a binding partner of the second polypeptide, and
(b) exposing the cells to a static magnetic field, thereby activating the ion channel and modulating the activity of the cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the method inhibits cell activity.

### Claim 3 (depends on 1)

The method of claim 1, wherein the method increases cell activity.

### Claim 4 (depends on 1)

The method of claim 1, wherein the metal binding protein is selected from the group consisting of ferritin, ferritin variants, and bacterioferritin.

### Claim 5 (depends on 1)

The method of claim 1, wherein the modulated cell activity is cell proliferation and/or differentiation, apoptosis, one or more signal transduction pathways, neuronal activation, or development of long-term potentiation and/or regulation of gene expression.