Intrapleural gene therapy for alpha-1 antitrypsin deficiency-related lung disease

Katie M. Stiles, Dolan Sondhi, Stephen M. Kaminsky, Bishnu P. De, Jonathan B. Rosenberg, Ronald Crystal

Research output: Contribution to journalReview article


Alpha-1 antitrypsin deficiency (AATD) manifests primarily as early-onset emphysema caused by the destruction of the lung by neutrophil elastase due to low amounts of the serine protease inhibitor alpha-1 antitrypsin (AAT). The current therapy involves weekly intravenous infusions of AAT-derived from pooled human plasma that is efficacious, yet costly. Gene therapy applications designed to provide constant levels of the AAT protein are currently under development. The challenge is for gene therapy to provide sufficient amounts of AAT to normalize the inhibitor level and anti-neutrophil elastase capacity in the lung. One strategy involves administration of an adeno-associated virus (AAV) gene therapy vector to the pleural space providing both local and systemic production of AAT to reach consistent therapeutic levels. This review focuses on the strategy, advantages, challenges, and updates for intrapleural administration of gene therapy vectors for the treatment of AATD.

Original languageEnglish
Pages (from-to)244-257
Number of pages14
JournalChronic Obstructive Pulmonary Diseases
Issue number4
Publication statusPublished - 1 Jan 2018



  • Adeno-asssociated virus vectors
  • Alpha-1 antitrypsin deficiency
  • Gene therapy

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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