Imaging reporters of transgene expression
Disclosed are compositions and methods for imaging in animals.
1. A method of visualizing a cell in a mammal-comprising:
a) administering a binding domain ligand into the mammal wherein:
(i) the binding domain ligand comprises;
(1) a label, and
(2) maltose, biotin, glutathione, or a hyaluran polymer;
(ii) the cell comprises a visualization molecule, comprising;
(1) a transmembrane domain, and
(2) a secretory or plasma membrane trafficking signal domain selected from the group consisting of HLA-B7, PDGFR, EGFR, IGFR, and Ig-k; and
(3) a hinge domain recognized by an endogenous protease selected from the group consisting of a complement protease or a serine protease, and
(4) an extracellular binding domain, wherein the binding domain ligand interacts with the binding domain, and
b) visualizing the label of the binding domain ligand.
2. The method of claim 1 , wherein the hinge domain comprises a factor IX site.
3. The method of claim 1 , wherein the visualization of the label is in real time.
4. The method of claim 1 , wherein the hinge domain is between the transmembrane domain and the binding domain ligand.
5. The method of claim 1 , wherein cleavage of the hinge domain allows for the binding domain ligand to be visualized.
6. The method of claim 1 , wherein the transmembrane domain comprises a single-pass or multi-pass transmembrane domain.
7. The method of claim 1 , wherein the binding domain is selected from a maltose binding protein, avidin, streptavidin, glutathione-S-transferase (GST), and cd-44.
8. The method of claim 1 , wherein the label comprises a fluorescent probe selected from the group consisting of cy5.5 or fitc, iodine, or gadolidium.
9. The method of claim 1 , wherein the visualization molecule further comprises multiple binding domains.
10. The method of claim 1 , wherein the visualization molecule further comprises an identification domain.
11. The method of claim 10 , wherein the identification domain comprises an epitope.
12. The method of claim 11 , wherein the epitope is selected from a hemagglutinin A epitope, a FLAG tag, and a myc epitope.
13. The method of claim 10 , further comprising a second identification domain.
14. The method of claim 1 , wherein the visualization of the label comprises performing a technique selected from non-invasive imaging, computed tomography, bioluminescence imaging, planar gamma camera imaging, single photon three-dimensional (3-D) emission computed tomography (SPECT) imaging, continuous-wavelength or time-domain light-based imaging, magnetic resonance imaging, fluorescence imaging, diffuse optical tomography, ultrasonography, Positron Emission Topography (PET) imaging, fluorescence correlation spectroscopy, in vivo two-photon microscopy, optical coherence tomography, speckle microscopy, nanocrystal labeling, and second harmonic imaging.
15. The method of claim 1 , wherein the mammal is used as a disease model, wherein the disease is cancer, Alzheimer's, Grave's disease, Parkinson's, cystic fibrosis, muscular dystrophy, diabetes, or hamartoma.
16. The method of claim 1 , wherein the visualization of the label identifies a tumor.
17. The method of claim 1 , wherein the visualization label allows for monitoring treatment of diseases selected from cancer, Alzheimer's, Grave's disease, Parkinson's, cystic fibrosis, muscular dystrophy, diabetes, and hamartoma.
18. The method of claim 1 , wherein the visualizing allows for cellular monitoring of transplanted cells.
19. The method of claim 18 , wherein the transplanted cells are selected from the group consisting of pluripotent stem cells, multi potent stem cells, monopotent stem cells, differentiated cells, hematopoietic cells, mesenchymal cells, muscle cells, pancreatic cells, or neural cells, or any combination thereof.
20. The method of claim 1 , wherein the visualization molecule is present in a subset of cells of the mammal.
21. The method of claim 1 , wherein the visualization molecule is expressed in tissue selected from the group consisting of preneoplastic, neoplastic, endodermal, ectodermal, or mesenchymal tissue.
22. The method of claim 1 , wherein expression of the visualization molecule is induced.
23. The method of claim 1 , wherein the visualization molecule is constitutively expressed.