0
Impact of Basic Research on Tomorrow's Medicine |

Gene Therapy for Pulmonary Diseases*

James West, PhD; David M. Rodman, MD
Author and Funding Information

*From the Department of Medicine, University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: David M. Rodman, MD, 4200 E. Ninth Ave, Box B-133, Denver, CO 80262; e-mail: david.rodman@uchsc.edu



Chest. 2001;119(2):613-617. doi:10.1378/chest.119.2.613
Text Size: A A A
Published online

Gene therapy for pulmonary disease has attracted a great deal of attention since the first report of successful gene delivery 10 years ago. Potential indications for gene therapy include chronic illnesses such as cystic fibrosis and α1-antitrypsin deficiency, and acute illnesses such as acute transplant rejection and chemotherapy-induced lung injury. The key technological impediment to successful gene therapy is vector optimization. Viral vectors, including adenovirus and adeno-associated virus, have relatively low efficiency in vivo. In addition, adenovirus has been associated with a brisk inflammatory response and limited duration of expression in the lung. Nonviral vectors, particularly liposomes, have also been tried, with limited expression efficiency and some toxicity. Although work is ongoing to improve adenoviral and adeno-associated viral vectors and test other viral and nonviral vectors, an ideal vector has not yet been identified. Several important barriers to successful gene therapy, including the host inflammatory response, promotor down-regulation, tissue-specific targeting, and physical barriers to gene delivery in the airway, will need to be overcome. Despite these daunting problems, several human gene therapy trials have been completed, using adenovirus, adeno-associated virus, and liposomes. In general, these trials have been focused on safety, and have shown that there is dose-dependent inflammation in response to adenovirus. Adeno-associated virus appears to cause little inflammation. Demonstration of successful gene delivery and transcription has been quite variable in human trials. In general, the level of expression of transgene appears to be quite low. In summary, although there is great promise for gene therapy in the lung, significant challenges remain in translating this technology to successful human therapy.


Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
Gene Editing and Genetic Lung Disease: Basic Research Meets Therapeutic Application. Am J Respir Cell Mol Biol Published online Oct 25, 2016;
The Mucus Barrier to Inhaled Gene Therapy. Mol Ther Published online Nov 01, 2016;
Guidelines
Infant/toddler pulmonary function tests-2008 revision & update.
American Association for Respiratory Care | 4/3/2009
Removal of the endotracheal tube—2007 revision & update.
American Association for Respiratory Care | 8/17/2007
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543