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In-vitro Mutagenesis

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.

Gene Therapy

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...

Gene Therapy

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...

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Related Experiment Video

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Stereotaxic Injection of a Viral Vector for Conditional Gene Manipulation in the Mouse Spinal Cord

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Spatial and temporal control of gene therapy using ionizing radiation

D E Hallahan¹, H J Mauceri, L P Seung

¹Department of Radiation and Cellular Oncology, University of Chicago, Illinois, USA.

Nature Medicine

|August 1, 1995

Summary

This study demonstrates that radiation can control gene transcription for cancer therapy. Combining radiation with a gene therapy vector delivering tumour necrosis factor-alpha (TNF-alpha) enhanced tumor control without increasing normal tissue damage.

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Area of Science:

Oncology
Molecular Biology
Radiotherapy

Background:

The Egr-1 gene's transcription is activated by X-rays via its promoter region.
Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with radiosensitizing and tumoricidal properties.

Purpose of the Study:

To investigate the spatial and temporal regulation of gene therapy using radiation-inducible promoters.
To evaluate the efficacy of delivering a tumour necrosis factor-alpha (TNF-alpha) gene construct regulated by the Egr-1 promoter in human tumors.

Main Methods:

A replication-deficient adenovirus (Ad5.Egr-TNF) was engineered to carry the Egr-1 promoter linked to the TNF-alpha gene.
This construct was delivered to human tumors grown in nude mice.
Mice received combined treatment with Ad5.Egr-TNF and 5,000 cGy (rad) radiation.

Main Results:

Combined treatment significantly increased intratumoral TNF-alpha production.
Enhanced tumor control was observed compared to Ad5.Egr-TNF or radiation alone.
Increased tumor control was achieved without exacerbating normal tissue damage.

Conclusions:

Controlling gene transcription with ionizing radiation in vivo offers a novel approach for gene-based cancer treatments.
This method allows for spatial and temporal regulation of therapeutic gene expression.
Radiation-inducible gene therapy holds promise for improving cancer treatment efficacy and safety.