A large number of diseases and disorder result from the dysfunction of a specific tissue or organ. A number of these are currently treated by transplantation, e.g. heart transplantation for certain types of cardiac dysfunction, corneal transplantation for endothelial cell dysfunction, stem cells for retinal neuroprotection, etc. However, transplantation procedures are invasive, have varying rates of success, and are not yet even available for many types of disease or disorders, in particular for a of eye diseases, for example, including diseases of the cornea (including but not limited to endothelial or stromal dystrophies), diseases of retinal ganglion cells and the optic nerve (including but not limited to glaucoma, ischemic optic neuropathies, other optic neuropathies), and diseases of retinal photoreceptors and retinal pigment epithelium (including but not limited to Leber's congenital amaurosis, retinitis pigmentosa and age-related macular degeneration)
Although in many cases it would seem desirable to administer new “healthy” cells, e.g. by injection or infusion, simply injecting such cells generally does not work as they do not remain localized and stick to or become incorporated into the patients' tissue. For example, healthy corneal endothelial cells are inefficiently incorporated into a patient's diseased cornea when injected into the anterior chamber of the eye (e.g. Mimura et al, Invest Ophthalmol. Vis. Sci. 2005, 46(10):3637-44), and healthy retinal ganglion cells are not incorporated into the retina when injected into the vitreous cavity of the eye. Most current technology depends on whole tissue transplants, or in the case of stem cell clinical trials, there are no techniques for controlling the cells' localization in vivo. A stem cell transplantation clinical trial for retinitis pigmentosa, for example, uses subretinal injection of hematopoetic stem cells, but does nothing to control their localization there, or keep them from floating or migrating away after surgical implantation. As another example, corneal endothelial cells injected into the anterior chamber of the eye will simply fall by gravity away from the cornea, and not properly attach. Thus there remains a need for new methods for targeting cells to specific tissues for therapeutic purposes.
Consigny (U.S. Pat. No. 6,203,487) described a method in which magnetic particles of micron size are inserted into cells for the purpose of focalized delivery. In the present application, a method of attaching magnetic nanoparticles with diameters of 500 nm or loss to the outer surface of cells delivering them to a target tissue is described. This is advantageous in many applications (e.g. applications involving the eye), because smaller particles that are not internalized into cells can be degraded from the cell surface and easily excreted after the cells have been situated. For example, in applications involving the eye, the particles can be excreted without clogging ocular outflow and thereby raising intraocular pressure.
USPTO Backgrounds
USPTO Backgrounds