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Related Concept Videos

Gene Therapy00:59

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 Therapy00:59

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...
The Parathyroid Glands00:59

The Parathyroid Glands

The two pairs of parathyroid glands embedded within the posterior surface of the thyroid gland are restricted by a dense capsule around them. These glands comprise two distinct cell populations—parathyroid oxyphil and parathyroid principal cells- pivotal in calcium homeostasis.
Oxyphil cells, whose functions remain elusive, emerge during late puberty, adding a layer of complexity to the parathyroid gland's intricacies. In contrast, principal parathyroid cells undertake a vital role by producing...

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Related Experiment Video

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Generation of Hypoparathyroid Rats via Carbon-Nanoparticle-Assisted Parathyroidectomy
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Experimental parathyroid hormone gene therapy using ØC31 integrase.

Sihoon Lee1, Soon Won Hong, Han Seok Choi

  • 1Department of Internal Medicine, Graduate School of Medicine, Gachon University of Medicine and Science, Namdong-gu, Incheon, Korea.

Endocrine Journal
|August 12, 2008
PubMed
Summary

This study demonstrates the successful site-specific integration of the parathyroid hormone (PTH) gene into mammalian genomes using the ØC31 integrase system. This advancement holds promise for developing effective gene therapies for conditions like hypoparathyroidism.

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Two Techniques to Create Hypoparathyroid Mice: Parathyroidectomy Using GFP Glands and Diphtheria-Toxin-Mediated Parathyroid Ablation

Published on: March 14, 2017

Area of Science:

  • Genetics
  • Molecular Biology
  • Gene Therapy

Background:

  • Hypoparathyroidism treatment traditionally involves calcium and vitamin D, but parathyroid hormone (PTH) replacement is a more physiologic option.
  • Current PTH synthesis is complex and expensive, creating a need for alternative therapeutic strategies.
  • Gene therapy offers a potential solution to overcome the limitations of traditional PTH replacement.

Purpose of the Study:

  • To investigate the efficacy of the ØC31 integrase system for site-specific genomic integration of the PTH gene.
  • To assess the expression and secretion of PTH following gene integration in vitro and in vivo.
  • To evaluate the potential of PTH gene therapy for hypoparathyroidism.

Main Methods:

  • Cotransfection of 293 HEK cells with PTH-attB plasmid and ØC31 integrase plasmid.
  • Assessment of PTH expression and secretion using immunoradiometric assays.
  • Hydrodynamic injection of PTH-attB plasmid into mice, followed by plasma PTH measurement and genomic DNA analysis for site-specific integration.

Main Results:

  • PTH was successfully expressed and secreted from both 293 HEK cells and mouse hepatocytes.
  • Pseudo-site analysis confirmed site-specific integration of the PTH cDNA into the host genomes in both in vitro and in vivo models.
  • The ØC31 integrase system demonstrated efficiency and site-specificity in integrating the PTH gene.

Conclusions:

  • The ØC31 integrase system is a viable tool for achieving site-specific genomic integration of therapeutic genes like PTH.
  • This technology shows significant potential for developing gene therapies, particularly for hypoparathyroidism.
  • Future research should focus on regulating PTH expression and secretion for successful clinical translation.