Granted Patent
B2
US 12,544,402 · App. 17/187,509 · Granted Feb 10, 2026
Targeted expression of microbial cholesterol catalysis genes reduces excess lipid
Inventors:
Mourad Topors (Scarborough, CA); Reason (Syracuse, NY); Guilherme Cherman Perdigão de Oliveira (Rio de Janeiro, BR); Marc Ridilla (Camillus, NY); Jayanta Mukherjee (Braintree, MA); David Mackenzie-Liu (Syracuse, NY); Garrett Strough (Lorraine, NY); David Thomas (Charlottesville, VA)
Assignee:
Repair Biotechnologies, Inc.
A61K35/12C12N9/0006C12N15/52C12N15/86C12Y101/01145C12Y114/15006C12Y118/01006C12Y503/03001C12N2750/14143C12Y101/03006
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Abstract
Disclosed herein are compositions, constructs, cassettes, vectors, cells, nucleic acids, peptides, proteins, protocols and methods for reducing cholesterol and lipid buildup in mammalian subjects, via gene and/or cell therapeutic treatments. In many embodiments, the disclosed compositions, cells, constructs, cassettes, vectors, nucleic acids, peptides, proteins, protocols and methods may help to reduce lipid levels in mammals. In one embodiment, the disclosed compositions, cells, constructs, cassettes, vectors, nucleic acids, peptides, proteins, protocols and methods are useful in reducing lipid build-up, especially cholesterol, in liver cells.
Claims (24)
1 . A method of reducing lipid concentration in at least one liver cell of a subject in need of treatment for a cholesterol related disease or condition, the method comprising the steps of:
contacting a vector comprising a construct with the liver cell of the subject, wherein the construct comprises a nucleic acid sequence of SEQ ID NO: 1 or 13;
allowing the construct to enter the liver cell of the subject and create a modified liver cell;
allowing the modified liver cell to degrade lipid within the modified cell and reduce the size of at least one atheroma in the subject, wherein the lipid is cholesterol and the atheroma is located at or near the aorta of the subject.
2 . The method of claim 1 , wherein the construct comprises SEQ ID NO: 1.
3 . The method of claim 2 , wherein the construct is a nucleic acid comprising a eukaryotic promoter sequence of CMV promoter sequence.
4 . The method of claim 2 , wherein the modified liver cell is a hepatocyte.
5 . The method of claim 4 , wherein the cholesterol related disease or condition is selected from one or more of atherosclerosis, cardiovascular disease (CVD), myocardial infarction, stroke, peripheral vascular disease, diabetes, hypothyroidism, kidney disease, liver disease, fatty liver, non-alcoholic fatty liver disease (NAFLD), obesity, nonalcoholic steatohepatitis (NASH), cirrhosis of the liver, hepatitis, and liver fibrosis.
6 . The method of claim 1 , wherein the liver cell of the subject is derived from a stem cell.
7 . The method of claim 6 , wherein the stem cell is an induced pluripotent stem cell.
8 . The method of claim 1 , wherein the liver cell of the subject is a differentiated mammalian liver cell.
9 . The method of claim 1 , wherein the modified liver cell is administered to the subject.
10 . The method of claim 5 , wherein the subject suffers from fatty liver or NAFLD.
11 . The method of claim 1 , wherein the modified liver cell is a hepatocyte within the liver of the subject.
12 . The method of claim 1 , wherein the vector is a viral vector.
13 . The method of claim 12 , wherein the vector contacts the liver cell of the subject within the subject.
14 . The method of claim 1 , wherein the vector is a lipid nanoparticle.
15 . The method of claim 14 , wherein the vector contacts the liver cell of the subject within the subject.
16 . A method of reducing lipid concentration in at least one target cell of a subject in need of treatment for atherosclerosis, the method comprising the steps of:
contacting a vector comprising a construct with a liver cell of the subject, wherein the construct comprises a nucleic acid sequence of SEQ ID NO:1;
allowing the construct to enter the liver cell of the subject and create a modified liver cell;
allowing the modified liver cell to degrade lipid in the modified liver cell, wherein the lipid is cholesterol;
reducing the lipid concentration in the at least one target cell, wherein the target cell is located in an atheroma of the subject and the modified liver cell is in the liver of the subject, and the subject suffers from type II, type III, type IV, and/or type V lesions or atheromas; and
reducing a size of at least one lesion or atheroma, wherein the atheroma is located at or near the aorta of the subject.
Assignments (2)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME PREVIOUSLY RECORDED AT REEL: 057457 FRAME: 0190. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT .
Recorded Sep 22, 2021
From: TOPORS, MOURAD; REASON, .; PERDIGÃO DE OLIVEIRA, GUILHERME CHERMAN; RIDILLA, MARC; MUKHERJEE, JAYANTA; MACKENZIE-LIU, DAVID; STROUGH, GARRETT; THOMAS, DAVID
To: REPAIR BIOTECHNOLOGIES, INC.
Reel/Frame 057569/0017 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 13, 2021
From: TOPORS, MOURAD; ., REASON; PERDIGÃO DE OLIVEIRA, GUILHERME CHERMAN; RIDILLA, MARC; MUKHERJEE, JAYANTA; MACKENZIE-LIU, DAVID; STROUGH, GARRETT; THOMAS, DAVID
To: REPAIR BEIOTECHNOLOGIES, INC.
Reel/Frame 057457/0190 →
Continuity (3)
Provisional Application
63094075
· Oct 20, 2020
Provisional Application
62983102
· Feb 28, 2020
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