MicroRNA in T cell activation

Patent metadata

Field	Value
Publication number	US-11266676-B2
Application number	US-201716345512-A
Country	US
Kind code	B2
Filing date	Oct 27, 2017
Priority date	Oct 27, 2016
Publication date	Mar 8, 2022
Grant date	Mar 8, 2022

Abstract

Disclosed herein are methods for treating an immune system condition and/or altering T cell activation in a subject. Also disclosed herein are methods for diagnosing an immune system condition in a subject. In some examples, the methods can include measuring expression of at least one T cell activation-related miRNA in a sample obtained from a subject. The methods further include administering to the subject a therapeutically effective amount of an miRNA or mimic thereof, and/or an inhibitor of miRNA or mimic thereof and/or administering to the subject T cells contacted with an effective amount of miRNA or mimic thereof, and/or an inhibitor of miRNA or mimic thereof.

First claim

I claim:

1. A method for altering T cell activation in a subject, comprising:
(a) selecting a subject with activated T cells; and
administering to the subject a therapeutically effective amount of:
(i) an inhibitor of miRNA or a-mimic of the inhibitor of miRNA, wherein the inhibitor of miRNA comprises a nucleic acid at least 90% complementary to an miRNA, wherein the miRNA comprises at least one of miR-7-1-3p, miR-128-3p, miR-26b-5p, miR-125b-5p, miR-363-3p, miR-25-3p, miR-629-3p, miR-330-3p, miR-501-3p, and/or miR-99a-5p; or
(ii) an miRNA, wherein the miRNA comprises at least one of mir-326, mir-6860, mir-1976, mir-550b-1, mir-550b-2, miR-8071, miR-4481, and/or mir-3689b, or a mimic thereof,
thereby increasing T cell activation as compared to a control; or

(b) selecting a subject with activated T cells; and
administering to the subject a therapeutically effective amount of:
(i) an miRNA, wherein the miRNA comprises at least one of miR-7-1-3p, miR-128-3p, miR-26b-5p, miR-125b-5p, miR-363-3p, miR-25-3p, miR-629-3p, miR-330-3p, miR-501-3p, and/or miR-99a-5p, or a mimic thereof; or
(ii) an inhibitor of miRNA or a mimic of the inhibitor of miRNA, wherein the inhibitor of miRNA comprises a nucleic acid at least 90% complementary to an miRNA, wherein the miRNA comprises at least one of mir-326, mir-6860, mir-1976, mir-550b-1, mir-550b-2, miR-8071, miR-4481, and/or mir-3689b,
thereby decreasing T cell activation as compared to a control.

2. A method for altering T cell activation in a subject comprising:
(a) activating T cells; and
contacting the activated T cells with an effective amount of:
(i) an inhibitor of miRNA or a-mimic of the inhibitor of miRNA, wherein the inhibitor of miRNA comprises a nucleic acid at least 90% complementary to an miRNA, wherein the miRNA comprises at least one of miR-7-1-3p, miR-128-3p, miR-26b-5p, miR-125b-5p, miR-363-3p, miR-25-3p, miR-629-3p, miR-330-3p, miR-501-3p, and/or miR-99a-5p; or
(ii) an miRNA, wherein the miRNA comprises at least one of mir-326, mir-6860, miR-6860, mir-1976, mir-550b-1, mir-550b-2, miR-8071, miR-4481, and/or mir-3689b, or a mimic thereof,
thereby increasing T cell activation as compared to a control; or

(b) contacting activated T cells with an effective amount of:
(i) an miRNA, wherein the miRNA comprises at least one of miR-7-1-3p, miR-128-3p, miR-26b-5p, miR-125b-5p, miR-363-3p, miR-25-3p, miR-629-3p, miR-330-3p, miR-501-3p, and/or miR-99a-5p, or a mimic thereof; or
(ii) an inhibitor of miRNA or a mimic of the inhibitor of miRNA, wherein the inhibitor of miRNA comprises a nucleic acid at least 90% complementary to an miRNA, wherein the miRNA comprises at least one of mir-326, mir-6860, miR-6860, mir-1976, mir-550b-1, mir-550b-2, miR-8071, miR-4481, and/or mir-3689b,

thereby decreasing the T cell activation as compared to a control.

3. The method of claim 1 , wherein the T cell comprises a CD4+ T cell, a CD8+ T cell, or a combination thereof.

4. The method of claim 1 , wherein:
(a) the inhibitor of miRNA or mimic of the inhibitor of miRNA inhibits at least one of miR-7-1-3p, miR-128-3p, miR-26b-5p, miR-125b-5p, and/or miR-363-3p; or
(b) the miRNA comprises a at least one of miR-7-1-3p, miR-128-3p, miR-26b-5p, miR-125b-5p, and/or miR-363-3p or a mimic thereof.

5. The method of claim 1 , wherein the miRNA comprises a pri-miRNA, a pre-miRNA, or a mature miRNA.

6. The method of claim 1 , wherein the miRNA is a human miRNA.

7. The method of claim 1 , wherein the subject is infected with human immunodeficiency virus, the subject has been or will be exposed to microgravity, or the subject has an inflammatory or autoimmune disorder.

8. The method of claim 7 , wherein the inflammatory disorder comprises rheumatoid arthritis, chronic obstructive pulmonary lung disease, inflammatory bowel disease, or systemic lupus erythematosus or wherein the autoimmune disorder comprises multiple sclerosis, ankylosing spondylitis, celiac disease, Crohn's disease, Graves' disease, Hashimoto thyroiditis, or autoimmune uveitis.

9. The method of claim 1 , wherein the subject is human.

Assignees

• Us Veterans Affairs
• Univ California
• Us Gov Veterans Affairs

Inventors

• Hughes-Fulford Millie

Classifications

• C12Q2600/178

  miRNA, siRNA or ncRNA · CPC title

• C12N2310/141

  MicroRNAs, miRNAs · CPC title

• A61K31/7105 Primary

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• C12N2330/10

  naturally occurring · CPC title

• C12Q1/6874

  involving nucleic acid arrays, e.g. sequencing by hybridisation · CPC title