# US 8,541,237 B2 · Method for diagnosing disease using adenovirus harboring trans-splicing ribozyme by molecular imaging

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- Number: US 8,541,237 B2
- Document ID: US8541237B2
- Status: Granted
- Kind: B2
- Application number: 12/522,597
- Filed: 2007-10-26
- Published: 2011-07-07
- Granted: 2013-09-24
- Earliest claimed: 2007-10-25
- Assignees: National Cancer Center
- Applicants: In-Hoo Kim; Seong-Wook Lee; Seung-Hee Hong; Jin-Sook Jeong; Yoon-Jong Lee; Yeon-Su Lee; Haeng-Im Jung
- Inventors: In-Hoo Kim; Seong-Wook Lee; Seung-Hee Hong; Jin-Sook Jeong; Yoon-Jong Lee; Yeon-Su Lee; Haeng-Im Jung
- Web page: https://patentgrep.com/patent/US8541237B2

## CPC

- A61K 49/0045: {the fluorescent agent being a peptide or protein used for imaging or diagnosis in vivo}
- A61P 35/00: Antineoplastic agents
- Y10T 436/143333: Saccharide [e.g., DNA, etc.]
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

Disclosed herein is a composition for molecular imaging comprising a trans-splicing ribozyme coupled with an imaging reporter gene. The trans-splicing ribozyme targets a specific gene associated with a disease. Also disclosed is a molecular imaging method using the composition.

## Claims

### Claim 1

A method for molecular imaging of cancer cells in a subject, the method comprising:
1) administering to a subject a trans-splicing ribozyme vector comprising a trans-splicing ribozyme specific to a target gene and an imaging reporter gene, wherein upon administration, the target gene is replaced with the imaging reporter gene through ribozyme-mediated trans-splicing so as to activate the imaging reporter gene; and
2) analyzing the activation of the imaging reporter gene through molecular imaging, wherein the trans-splicing ribozyme is a modified form of a trans-splicing group I ribozyme and comprises:
i) an antisense sequence complementary to a region downstream of the uridine residue at position +45 of the target mouse cytoskeleton-associated protein 2 (mCKAP2) RNA, the antisense sequence consisting of 83 nucleotides complementary to nucleotides at positions +59 to +141 of mCKAP2 RNA or 300 nucleotides complementary to nucleotides at positions +59 to +358 of mCKAP2 RNA;
ii) a P1 helix region linked to the 3′ end of the antisense sequence which comprises an internal guide sequence (IGS), 5′-GAGCGT-3′;
iii) a P10 helix region linked to the 3′ end of the P1 helix region; and
iv) a sequence linked to the 3′ end of the P10 helix region and encoding β-galactosidase (lacZ) or luciferase (luc).

### Claim 2 (depends on 1)

The method according to claim 1, wherein the vector is an adenovirus vector.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the vector has a genetic map shown in FIG. 2.