Current status of gene therapy for alpha-1 antitrypsin deficiency

UMMS Affiliation

Gene Therapy Center; Department of Pediatrics, Division of Pulmonology

Publication Date


Document Type



Adenoviridae; Animals; Clinical Trials as Topic; Genetic Therapy; Genetic Vectors; Humans; Transgenes; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency


Genetics and Genomics | Respiratory Tract Diseases | Therapeutics | Translational Medical Research


INTRODUCTION: As a common monogenic disease, alpha-1 antitrypsin (AAT) deficiency has undergone thorough investigation for the development of gene therapy. The most common pathology associated with AAT deficiency occurs in the lung, where the loss of function due to impaired secretion of mutant AAT prevents the inhibition of neutrophil elastase and leads to loss of elastin content from the alveolar interstitium.

AREAS COVERED: Current treatment in the USA consists of recurrent intravenous protein replacement therapy to augment serum AAT levels. In an attempt to replace recurring treatments with a single dose of gene therapy, recombinant adenovirus, plasmid, and recombinant adeno-associated virus (rAAV) vectors have been investigated as vectors for transgene delivery.

EXPERT OPINION: Large strides in gene therapy for AAT deficiency lung disease have led to the development of rAAV1-AAT capable of producing sustained serum AAT levels in clinical trials after intramuscular administration in humans at 3% of the target level. Further increases in levels are anticipated as limb perfusion targets greater muscle mass. The future roles of intrapleural and airway delivery, miRNA-expressing vectors, iPS cell platforms, and genome editing are anticipated.


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DOI of Published Version



Expert Opin Biol Ther. 2015 Mar;15(3):329-36. doi: 10.1517/14712598.2015.978854. Link to article on publisher's site. Epub 2014 Nov 3.

Journal/Book/Conference Title

Expert opinion on biological therapy

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Link to Article in PubMed

PubMed ID