Intrapleural 'outside-in' gene therapy: Therapeutics for organs of the chest via gene transfer to the pleura

Adriana Heguy, Ronald Crystal

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

The pleural space is an attractive site for using viral vectors to deliver gene products to the lung parenchyma, other thoracic structures and the systemic circulation. The advantages of intrapleural gene transfer using viral vectors include: (i) easy accessibility; (ii) large surface area; (iii) ability to provide high concentrations of secreted gene products to chest structures; (iv) low risk of detrimental effects of possible vector-induced inflammation compared with intravascular delivery; and (v) because it is local, lower vector doses can be used to deliver therapeutic genes to thoracic structures than less efficient systemic routes. Examples of pleural gene transfer include the use of adenovirus vectors to treat mesothelioma by transiently expressing genes that encode toxic proteins, immunomodulatory molecules or anti-angiogenesis factors. Intrapleural delivery of adeno-associated viral vectors represents an efficient strategy to treat α1-antitrypsin (α1AT) deficiency, achieving high lung and systemic therapeutic levels of α1AT. Intrapleural delivery of gene transfer vectors holds promise for the treatment of diseases requiring transient, localized gene expression, as well as sustained expression of genes to correct hereditary disorders requiring localized or systemic expression of the therapeutic protein.

Original languageEnglish
Pages (from-to)440-453
Number of pages14
JournalCurrent Opinion in Molecular Therapeutics
Volume7
Issue number5
Publication statusPublished - 1 Oct 2005
Externally publishedYes

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Keywords

  • α-antitrypsin deficiency
  • Adeno-associated virus
  • Adenovirus
  • Gene therapy
  • Mesothelioma
  • Pleura

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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