# US 2022/0033792 A1 · Methods and compositions for cellular reprogramming

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2022/0033792 A1
- Document ID: US20220033792A1
- Status: Published application
- Kind: A1
- Application number: 17/230,798
- Filed: 2021-04-14
- Published: 2022-02-03
- Earliest claimed: 2016-11-03
- Assignees: Youhealth Biotech, Limited; The Regents of the University of California
- Applicants: Youhealth Biotech, Limited; The Regents of the University of California
- Inventors: Kang ZHANG; Rui HOU; Gen LI
- Web page: https://patentgrep.com/patent/US20220033792A1

## CPC

- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- C12N 9/222: {Clustered regularly interspaced short palindromic repeats [CRISPR]-associated [CAS] enzymes}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61P 7/06: Antianaemics
- A61P 27/02: Ophthalmic agents
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C12N 5/0621: {Eye cells, e.g. cornea, iris pigmented cells (photoreceptors C12N5/062)}
- C12N 15/8509: {for producing genetically modified animals, e.g. transgenic}
- C12N 15/907: {in mammalian cells}
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2800/40: Systems of functionally co-operating vectors
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed herein are methods and pharmaceutical compositions for the treatment of retinitis pigmentosa, macular degeneration and other retinal conditions by interfering with expression of genes, such as those encoding photoreceptor cell-specific nuclear receptor and neural retina-specific leucine zipper protein, in cells of the eye. These methods and compositions employ nucleic acid based therapies.

## Claims

### Claim 1

A method of re-programming a cell from a first cell type to a second cell type, comprising contacting the cell with:
a) a guide RNA that hybridizes to a target site of a gene, wherein the gene encodes a protein that contributes to a cell type specific function of the cell; and
b) a Cas nuclease, or polynucleotide encoding the Cas nuclease, wherein the Cas nuclease cleaves a strand of the gene at the target site,
wherein cleaving the strand modifies expression of the gene such that the cell can no longer perform the cell type specific function, thereby re-programming the cell to the second cell type.

### Claim 2 (depends on 1)

The method of claim 1, wherein the gene comprises a mutation that causes a detrimental effect in the first cell type, wherein the detrimental effect is selected from senescence, apoptosis, lack of differentiation, and aberrant cellular proliferation.

### Claim at position 3

-7. (canceled)

### Claim 8 (depends on 1)

The method of claim 1, wherein the cell is a retinal cell.

### Claim 9 (depends on 1)

The method of claim 1, wherein the first cell type is a rod and the second cell type is a cone.

### Claim 10 (depends on 1)

The method of claim 1, wherein the cell type specific function is night vision or color vision

### Claim 11 (depends on 1)

The method of claim 1, wherein the first cell type is a colon cancer cell and the second cell type is a benign intestinal or colon cell, and wherein the gene is selected from APC, MYH1, MYH2, MYH3, MLH1, MSH2, MSH6, PMS2, EPCAM, POLE1, POLD1, NTHL1, BMPR1A, SMAD4, PTEN, and STK11.

### Claim 12 (depends on 1)

The method of claim 1, wherein the first cell type is a malignant B cell and the second cell type is a benign macrophage, and wherein the gene is selected from C-MYC, CCND1, BCL2, BCL6, TP53, CDKN2A, and CDI9.

### Claim 13 (depends on 1)

The method of claim 1, wherein the first cell type is a neuron and the second cell type is a glial cell, and wherein the gene is selected from APP and MAPT.

### Claim 14 (depends on 1)

The method of claim 1, wherein the first cell type is a glial cell and the second cell type is a dopamine producing neuron, and wherein the gene is selected from SNCA, LRRK2, P ARK2, PARK7, and PINK1.

### Claim 15

A method of treating an eye condition comprising administering to a subject in need thereof:
a) a first guide RNA that hybridizes to a target site of a gene in a first type of cell, wherein the gene encodes a protein that contributes to a first function of the first type of cell; and
b) a Cas nuclease that cleaves a strand of the gene at the target site, wherein cleaving the strand modifies expression of the gene such that the first type of cell is switched from a first type of cell to a second type of cell, wherein a resulting presence or increase in the second type of cell improves the eye condition.

### Claim 16 (depends on 15)

The method of claim 15, wherein modifying expression of the gene comprises reducing expression of the gene in the first type of cell by at least about 90%.

### Claim 17 (depends on 15)

The method of claim 15, wherein modifying expression of the gene comprises editing the gene, wherein the editing results in production of no protein from the gene or a non-functional protein from the gene.

### Claim 18 (depends on 15)

The method of claim 15, wherein the first type of eye cell is a rod and the second type of eye cell is a cone.

### Claim 19 (depends on 15)

The method of claim 15, wherein the eye condition is retinal degeneration, retinitis pigmentosa or macular degeneration.

### Claim 20 (depends on 15)

The method of claim 15, wherein the gene is selected from NRL, NR2E3, GNATI, ROR beta, OTX2, CRX and THRB.

### Claim 21 (depends on 1)

A method of treating an eye condition in a subject in need thereof with are programmed cell, wherein the re-programmed cell is produced by the method of claim 1.

### Claim 22 (depends on 21)

The method of claim 21, wherein the re-programmed cell is autologous to the subject.

### Claim 23 (depends on 21)

The method of claim 21, wherein the condition is selected from macular degeneration, retinitis pigmentosa, and glaucoma.

### Claim 24 (depends on 21)

The method of claim 21, wherein the gene is selected from NRL, NR2E3, GNAT1, ROR beta, OTX2, CRX and THRB.

### Claim at position 21

-30. (canceled)