Lentiviral vector gene therapy protects XCGD mice from acute staphylococcus aureus pneumonia and inflammatory response

Giada Farinelli, Raisa Jofra Hernandez, Alice Rossi, Serena Ranucci, Francesca Sanvito, Maddalena Migliavacca, Chiara Brombin, Aleksandar Pramov, Clelia Di Serio, Chiara Bovolenta, Bernhard Gentner, Alessandra Bragonzi, Alessandro Aiuti

Research output: Contribution to journalArticlepeer-review


Chronic granulomatous disease (CGD) is a primary immunodeficiency due to a deficiency in one of the subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. CGD patients are characterized by an increased susceptibility to bacterial and fungal infections, and to granuloma formation due to the excessive inflammatory responses. Several gene therapy approaches with lentiviral vectors have been proposed but there is a lack of in vivo data on the ability to control infections and inflammation. We set up a mouse model of acute infection that closely mimic the airway infection in CGD patients. It involved an intratracheal injection of a methicillin-sensitive reference strain of S. aureus. Gene therapy, with hematopoietic stem cells transduced with regulated lentiviral vectors, restored the functional activity of NADPH oxidase complex (with 20-98% of dihydrorhodamine positive granulocytes and monocytes) and saved mice from death caused by S. aureus, significantly reducing the bacterial load and lung damage, similarly to WT mice even at low vector copy number. When challenged, gene therapy-treated XCGD mice showed correction of proinflammatory cytokines and chemokine imbalance at levels that were comparable to WT. Examined together, our results support the clinical development of gene therapy protocols using lentiviral vectors for the protection against infections and inflammation.
Original languageEnglish
Pages (from-to)1873 - 1880
Number of pages8
JournalMolecular Therapy
Issue number10
Publication statusPublished - Oct 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


Dive into the research topics of 'Lentiviral vector gene therapy protects XCGD mice from acute staphylococcus aureus pneumonia and inflammatory response'. Together they form a unique fingerprint.

Cite this