Experimental parathyroid hormone gene therapy using ØC31 integrase

Sihoon Lee, Soon Won Hong, Han Seok Choi, Lee Young Lee, Chunja Nam, Yumie Rhee, Ung Il Chung, Sung Kil Lim

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


ØC31 integrase can integrate targeted plasmid DNA into preferred locations in mammalian genomes, resulting in robust, long-term expression of the integrated transgene. This system represents an effective tool that opens up promising possibilities for gene therapy. The classical treatment for hypoparathyroidism was calcium and vitamin D replacement. Recently, parathyroid hormone (PTH) replacement was reported to be a more potentially physiologic treatment option. However, PTH synthesis is technically difficult and costly. These issues may be minimized by using PTH gene therapy. We attempted to achieve site-specific genomic integration of the PTH gene into a human cell line and mice using this system. We cotransfected 293 HEK cells with PTH-attB plasmid with or without ØC31 integrase plasmid. Expression and secretion of PTH into culture supernatants and site-specific genomic integration of PTH cDNA were assessed by immunoradiometric assays and pseudo-site analysis, respectively. In in vivo experiments, we injected the PTH-attB plasmid with or without ØC31 integrase plasmid into a mouse tail vein using the hydrodynamic method. Plasma PTH concentrations were serially measured, and site-specific integration of PTH cDNA into the mouse genome was confirmed by examining hepatic genomic DNA. PTH was expressed and secreted from 293 HEK cells and mouse hepatocytes, and pseudo-site analysis confirmed the site-specific integration of PTH cDNA into the host genomes. The site-specificity and efficiency of this system are advantageous in many areas, including, potentially, gene therapy. PTH gene therapy is one candidate; however, for clinical applications, we need to regulate PTH expression and secretion in the future.

Original languageEnglish
Pages (from-to)1033-1041
Number of pages9
JournalEndocrine Journal
Issue number6
Publication statusPublished - 2008

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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