Stereotactic injection of adenoviral vectors that target gene expression to specific pituitary cell types: Implications for gene therapy

Eunjig Lee, Bayar Thimmapaya, J. Larry Jameson

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

OBJECTIVE: Gene therapy is a potentially useful strategy for the treatment of pituitary adenomas or hormone deficiency disorders. We investigated the feasibility of targeting gene expression to specific pituitary cell types in vivo, using a combination of stereotactic injection and adenoviral vectors that carry pituitary-specific promoters. METHODS: Recombinant adenoviruses containing the human growth hormone promoter (AdGHGal) or the human glycoprotein hormone α-subunit promoter (AdαGal) were used to drive expression of the β-galactosidase gene. The expression of β-galactosidase activity in the pituitary was analyzed after the administration of recombinant adenoviruses via the peripheral vein or the carotid artery, or by stereotactic injection into the rat pituitary. Double-label histology was used to evaluate cell-type expression in the pituitary. RESULTS: Intravascular injection of AdGHGal or AdαGal failed to deliver the marker gene to the pituitary. However, direct stereotactic injection of recombinant adenoviral vectors into the pituitary achieved a high level of transgene expression. In addition, immunohistochemical staining revealed selective expression of the AdGHGal or AdαGal transgenes in pituitary cells that normally produce the respective hormones. CONCLUSION: These findings indicate that adenoviral vectors carrying pituitary gland-specific promoters may be useful for targeted gene therapy of pituitary diseases. However, because of low transduction after peripheral administration, stereotactic injection or local administration of viruses at the time of pituitary surgery is probably required for efficient gene expression.

Original languageEnglish
Pages (from-to)1461-1469
Number of pages9
JournalNeurosurgery
Volume46
Issue number6
DOIs
Publication statusPublished - 2000 Jan 1

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Genetic Therapy
Gene Expression
Injections
Galactosidases
Transgenes
Adenoviridae
Hormones
Pituitary Diseases
Pituitary Hormones
Human Growth Hormone
Pituitary Neoplasms
Pituitary Gland
Carotid Arteries
Veins
Histology
Glycoproteins
Staining and Labeling
Viruses
Genes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

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Stereotactic injection of adenoviral vectors that target gene expression to specific pituitary cell types : Implications for gene therapy. / Lee, Eunjig; Thimmapaya, Bayar; Jameson, J. Larry.

In: Neurosurgery, Vol. 46, No. 6, 01.01.2000, p. 1461-1469.

Research output: Contribution to journalArticle

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