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Methods and composition related to in vivo imaging of gene expression

A technology of receptors and tissues, applied in preparations for in vivo experiments, chemical instruments and methods, biochemical equipment and methods, etc., can solve problems such as restrictions, non-targeting target tissues, radiopharmaceuticals that are not known to be safe, etc.

Inactive Publication Date: 2008-04-30
BOARD OF RGT THE UNIV OF TEXAS SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

A problem with many of these methods is that they employ radiopharmaceuticals that are not known to be safe for use in humans, or they use radioisotopes in ways that may have unforeseen adverse results
Another issue is that these methods are limited, as transcription of the reporter may be limited due to suboptimal promoter function
Additionally, imaging may not target the tissue of interest, such as tumors

Method used

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  • Methods and composition related to in vivo imaging of gene expression
  • Methods and composition related to in vivo imaging of gene expression
  • Methods and composition related to in vivo imaging of gene expression

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0257] Through functional and anatomical imaging to

[0258] Non-invasively quantify exogenous gene expression

[0259]The aim of this study was to evaluate whether a combination of functional (planar and SPECT imaging) and anatomical (MR) techniques could be used to non-invasively quantify tumor expression of somatostatin receptor type 2 (SSTR2) gene chimeras in vivo .

[0260] Materials and methods

[0261] plasmid

[0262] Full-length human SSTR2A was inserted into the pDisplay vector (Invitrogen, Carlsbad, CA) as described in Kundra et al., 2002 (the entire contents of which are expressly incorporated herein by reference for this section as well as the entire patent application), at the membrane localization sequence and Downstream of the hemagglutinin A (HA) epitope tag sequence.

[0263] Cell line generation and characterization

[0264] HT1080 cells (human fibrosarcoma, ATCC, Rockville, MD) were grown in Dulbecco's modified Eagle's medium (DMEM) containing 1x glu...

Embodiment 2

[0297] for therapeutic gene expression and molecular imaging

[0298] Development of Tumor Selective hTMC Plasmid Vector

[0299] A major obstacle to successful cancer gene therapy is the lack of effective delivery systems that can specifically target tumors. One approach for targeting transgene expression in tumors is to control gene expression via tumor-specific promoters. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is highly active in immortalized cells and in more than 85% of human cancers, but is quiescent in most normal somatic cells (Shay and Bacchetti, 1997; Shay et al., 2001). The hTERT promoter has been cloned and shown to selectively promote transgene expression in tumors but not in normal cells (Nakayama et al., 1998). However, like most other intrinsic mammalian promoters, the transcriptional promotion strength of the hTERT promoter is much weaker than commonly used viral promoters such as CMV and SV40 early promoters. ...

Embodiment 3

[0302] γ-camera imaging of gene transfer in vivo

[0303] Many molecular imaging methods for monitoring gene transfer in vivo rely on the sensitivity of gamma-camera, SPECT, or PET imaging to detect intravenously injected, radiolabeled compounds localized to the products of transferred genes, but most are both The gene of interest is not detected directly nor is FDA-approved radiopharmaceuticals for systemic use (Yamada et al., 1992; Kundra et al., 2002). radiopharmaceutical 111 In-octreotide has successfully detected cell surface membrane localization of SSTR2A product in HT1080 cells. The cell membrane localization of the product in HT1080 cells transfected with a plasmid expressing HA-SSTR2A (pHA-SSTA2A) was confirmed by immunofluorescence analysis using an anti-HA antibody (Fig. 9A). Injection into mice bearing HT1080 tumors generated by pHA-SSTR2A-transfectants 111 In-octreotide was used for biodistribution and imaging studies by gamma-camera (Fig. 9B). SSTR2A express...

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Abstract

Disclosed are nucleic acid sequences encoding a recombinant seven transmembrane G-protein associated receptor (GPCR) amino acid sequence operatively coupled to a tissue-selective promoter sequence. Also disclosed are methods of imaging or treating cells in a subject that involve introducing a nucleic acid encoding a reporter detectable in vivo using non-invasive methods operatively coupled to a tissue-selective promoter or amplified tissue specific promoter to the subject, and subjecting the subject to a non-invasive imaging technique or a therapeutic that selectively interacts with the reporter or gene of interest. For example, the subject may be a subject with cancer, and the therapeutic may be an anti-cancer agent. In particular, the hTERT promoter or amplified hTERT promoter drives expression of a reporter such hSSTR2 and / or hSSTR2 derivative) and these may be linked to a gene of interest. Imaging may be performed by a variety of methods including nuclear medicine.

Description

Background of the invention [0001] This application is related to US Provisional Patent Application 60 / 659,844, filed March 9, 2005, which is hereby incorporated by reference in its entirety. 1. Background of the invention [0002] The present invention relates generally to the fields of imaging, biomedical imaging, molecular biology, gene therapy and cancer therapy. Aspects of the invention include compositions and methods for non-invasive imaging and / or treatment of a subject. A further aspect of the invention includes a reporter molecule (which can be linked to a gene of interest) operably linked to the amplified tissue-specific promoter. Further aspects of the invention include novel nucleic acid sequences encoding recombinant 7-transmembrane G protein-coupled receptor (GPCR) amino acid sequences operably coupled to tissue-selective promoter sequences or amplified Amplified tissue specific promoters, including but not limited to hTERT and its derivatives. [0003] 2. ...

Claims

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Application Information

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IPC IPC(8): C12N15/85C07K14/705A61K49/00
CPCC12N2830/85A61K49/0002C12N2830/15C12N2830/60C12N2830/008C12N15/85C12N2840/203A61K49/00C07K14/705
Inventor V·库恩德拉B·方L·X·基D·杨
Owner BOARD OF RGT THE UNIV OF TEXAS SYST
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