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GSJ: Received Apr. 24, 2007: http://wbabin.net/saba/saba75.htm

Cell Type-Specific Nuclear Magnetic Resonance (NMR)

James Saba

Herein is described a means of cell type-specific imaging, such as NMR, in a living organism.

In essence the invention involves one or more particular types of cells, say in a mouse brain, expressing a protein or nucleic acid aptamer with high affinity and selectivity for an element which is rare or not normally found in cells.

For use in NMR, this element preferably has a high magnetic moment and distinct response frequency. Perhaps Scandium or Rubidium would work, and if not there are numerous to choose from.

A key to this process is the protein or aptamer which has the high affinity and selectivity to the selected element, and here it is suggested that such a protein or aptamer could be readily obtained by screening libraries with the radioactive element.

Libraries could be via phage or bacteria, or could be derived in vitro (1). Microarray or bead screening formats are preferred, as is detection by scintillation proximity (2,3).

As an alternative to NMR, other forms of imaging such as PET could be effected by using a radioactive element in the process described above.

In the near future it is anticipated that the genome of a mouse could be knocked-in with the required cell-type specific expression vector. However in a fully developed organism, human particularly, a targeted DNA or RNA expressing the required protein or aptamer could be utilized. Indeed, in the broadest scope of the invention, even targeting the synthesized protein or aptamer element-binding site may be novel.

It is also conceivable that the NMR frequency response of the element could be different dependent on its binding to the protein or aptamer; and that element binding by the protein or aptamer may inturn be dependent on the presence of another element or molecule (such as calcium). In such a case activity based NMR would appear possible.

Lastly, it is not unimaginable that subcellular imaging could be achieved.

If it should be that the above invention is indeed novel any patentable rights I may have, I freely give away.

It is hoped that others will honor the invention as delineated above and by the following claims.

Claims

1) A process for cell selective NMR or PET wherein said cell expresses a protein or aptamer not normally found in the cell.

2) A process of cell selective imaging where said cells expresses a bioengineered protein or aptamer which selectively binds an element which is rare or not normally found in the cell.

3) The process of claim 2 where the imaging is NMR.

4) The process of claim 2 where the element is radioactive.

5) The process of claim 4 where the imaging is PET

6) An engineered cell which expresses a protein or aptamer which selectively binds an element which is rare or not normally found in the cell.

7) Any imaging process which utilizes a nucleic acid expressing a protein or aptamer (or the isolated protein or aptamer) which binds an element which is rare or absent from cells and functions as a target for the imaging process

8) Claim 7 wherein the imaging process is NMR.

9) Claim 7 wherein the imaging process is PET.

10) Claim 7 where the protein or aptamer is administered to a human.

11) Claim 7 where the nucleic acid expressing said protein or aptamer is administered to a human.

12) Any of claims 7-11 wherein the protein or aptamer is isolated from an expression library.

13) Claim 12, where the expression library is phage or bacteria based.

14) Claim 12, where the expression library is derived in vitro.

References

1) Microarray of Polypeptides, via Simultaneous in vitroTranslation of Arrayed mRNAs (See numerous references herein).
Saba, J Gen Sci J Jan 26, 2005

2) Isolation of Enantiomer-binding Proteins, via Microarrays or Beads, and Scintillation Proximity.
Saba, J Gen Sci J June 3, 2005

3) Ligand Receptor Discovery Utilizing Radiolabeled Ligands, Microarrays, and Radiosensitive Materials.
Saba, J Gen Sci J Jan. 5, 2006

Addendum 5/5/07:

As an alternative to using a naked element for NMR, one could use a complexed element, for example by chelation. This complex being recognized by the protein or aptamer expressed in the cell.

Using a complexed NMR element allows other methods of screening libraries of proteins and aptamers for binders of the complexed element. For example one could conjugate the complex, perhaps via an organic linker, to a affinity column matrix or fluorescent dye.

For a complete list of articles published by James Saba in the Gen Sci J, please go to http://www.wbabin.net/saba.htm