Methods and system for optogenetic stimulation of adipocytes
AssigneeMaineHealth
InventorAaron C. Brown
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Abstract
Provided herein are, inter alia, methods, compositions, and kits for inducing thermogenesis in adipocyte populations. Also included are methods and compositions for increasing thermogenesis in adipocyte populations (e.g., brown/beige/white adipocyte populations) in a subject, as well as methods and compositions for treating subjects who are overweight, obese, or who have diabetes.
Claims112
A cell comprising at least one non-native gene or gene cassette encoding one or more adenylyl cyclase enzymes, wherein the adenylyl cyclase enzyme comprises an optogenetic moiety.
The cell of any one of the previous claims, wherein the adenylyl cyclase enzyme is from a strain of Naegleria australiensis, Pseudanabaena, Pseudanabaena yagii, Beggiatoa, Planktothrix, Pseudanabaena, Oxynema aestuarii, Cyanobacteria bacterium, Eutreptiella gymnastica, Eutreptia viridis, Euglena stellate, Colacium sideropus, Euglena quartana, Euglena gracilis, Oscillatoria acuminate and Euglena longa (Euglenophycean alga) (Astasia longa).
The cell of any one of the previous claims, wherein the amino acid sequence of the adenylyl cyclase enzyme comprises one or more amino acid substitutions relative to a wild type adenylyl cyclase sequence.
The cell of any one of the previous claims, wherein the gene or gene cassette encoding the adenylyl cyclase enzyme comprises an amino acid sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to, comprises, or consists of any one of SEQ ID NOs:
- 32, 33, or 62.
The cell of any one of the previous claims, wherein the gene or gene cassette encoding the adenylyl cyclase enzyme comprises an amino acid sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to, comprises, or consists of SEQ ID NOs:
- 1, 2, or 31.
The cell of any one of the previous claims, wherein the gene or gene cassette encoding the adenylyl cyclase enzyme comprising the optogenetic moiety is codon optimized for expression in a mammalian cell.
The cell of any one of the previous claims, wherein the cell is a mammalian cell.
The cell of any one of the previous claims, wherein the cell is a pluripotent stem cell.
A system for activating uncoupling protein-1 (UCP-1) in a cell, the system comprising:
- a) a delivery vector comprising a non-native nucleotide sequence encoding one or more adenylyl cyclase enzymes, wherein the adenylyl cyclase enzyme comprises an optogenetic moiety, wherein the delivery vector provides for delivery of the one or more adenylyl cyclase enzymes comprising the optogenetic moiety to a cell;
- b) a light source;
- and
- c) a control device.
A system for increasing the levels of uncoupling protein-1 (UCP-1) in a cell, the system comprising:
- a) a delivery vector comprising a non-native nucleotide sequence encoding one or more adenylyl cyclase enzymes, wherein the adenylyl cyclase enzyme comprises an optogenetic moiety, wherein the delivery vector provides for delivery of the one or more adenylyl cyclase enzymes comprising the optogenetic moiety to a cell;
- b) a light source;
- and
- c) a control device.
A method of treating a subject in need thereof, the method comprising:
- a) administering to a cell of the subject a nucleic acid encoding one or more adenylyl cyclase enzymes, wherein the adenylyl cyclase enzyme comprises an optogenetic moiety;
- b) activating the optogenetic moiety with a light source, wherein the adenylyl cyclase enzyme is activated, and wherein the light source is controlled by a control device;
- thereby treating the subject.
Dependencies are inferred from the claim text.