Barriers to inhaled gene therapy of obstructive lung diseases: A review

Namho Kim; Gregg A Duncan; Justin Hanes; Jung Soo Suk

doi:10.1016/j.jconrel.2016.05.031

Barriers to inhaled gene therapy of obstructive lung diseases: A review

J Control Release. 2016 Oct 28:240:465-488. doi: 10.1016/j.jconrel.2016.05.031. Epub 2016 May 16.

Authors

Namho Kim¹, Gregg A Duncan², Justin Hanes³, Jung Soo Suk⁴

Affiliations

¹ The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
² The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
³ The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Environmental and Health Sciences, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neurosurgery, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD 21205, USA.
⁴ The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: jsuk@jhmi.edu.

Abstract

Knowledge of genetic origins of obstructive lung diseases has made inhaled gene therapy an attractive alternative to the current standards of care that are limited to managing disease symptoms. Initial lung gene therapy clinical trials occurred in the early 1990s following the discovery of the genetic defect responsible for cystic fibrosis (CF), a monogenic disorder. However, despite over two decades of intensive effort, gene therapy has yet to help patients with CF or any other obstructive lung disease. The slow progress is due in part to poor understanding of the biological barriers to inhaled gene therapy. Encouragingly, clinical trials have shown that inhaled gene therapy with various viral vectors and non-viral gene vectors is well tolerated by patients, and continued research has provided valuable lessons and resources that may lead to future success of this therapeutic strategy. In this review, we first introduce representative obstructive lung diseases and examine limitations of currently available therapeutic options. We then review key components for successful execution of inhaled gene therapy, including gene delivery systems, primary physiological barriers and strategies to overcome them, and advances in preclinical disease models with which the most promising systems may be identified for human clinical trials.

Keywords: Biological barrier; Gene delivery vector; Preclinical model; Respiratory gene therapy.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae / genetics
Administration, Inhalation
Animals
Cell Line
Disease Models, Animal
Drug Carriers / chemistry
Gene Transfer Techniques*
Genetic Therapy / methods*
Genetic Vectors
Humans
Lung Diseases, Obstructive / genetics
Lung Diseases, Obstructive / therapy*
Retroviridae / genetics

Substances

Drug Carriers

Abstract

Publication types

MeSH terms

Substances

Grants and funding