Gene therapy for lung diseases: development in the vector biology and novel concepts for gene therapy applications

Our plain-English summary of Gene therapy for lung diseases: development in the vector biology and novel concepts for gene therapy applications, by M. Suzuki, T. Matsuse, Y. Isigatsubo (Current Molecular Medicine, 2001).

The study

• Authors: M. Suzuki, T. Matsuse, Y. Isigatsubo
• Journal: Current Molecular Medicine
• Published: 2001;1(1):67-79
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The lung represents an attractive target organ for somatic gene therapy strategy in that, (1) it is easily accessible by vectors, (2) most frequent hereditary disorders, cystic fibrosis (CF) and alpha1-antitrypsin deficiency (alpha1AT), occur in the lung, and (3) carcinoma of the lung is apparently a most common cause of death in humans. To date, approximately 400 clinical protocols for human gene therapy have been approved, and approximately 10% of the protocols target lung diseases such as cystic fibrosis (CF) and lung cancer. Currently available data from some of these human trials have successfully demonstrated that gene transfer to the human lung is possible, and that the strategy of overexpressing exogenous genes for curing or controlling lung diseases is potentially promising. In this manuscript, focusing on gene therapy of lung disorders, we aim to give an overview of the hurdles of current gene transfer strategies to overcome, then and also we aim to review recent, remarkable progresses in the vector biology that are potentially promising to maximize safety and efficiency of gene therapy. In addition, based on the most recent advances in the understanding of the molecular biological aspects of the pathogenesis of lung cancer, asthma, pulmonary fibrosis, and acute lung injury, novel therapeutic strategies of gene therapy for inflammatory and malignant diseases of the lung are discussed.

In plain English

This article was a review, not an original study. The authors reviewed published work on gene therapy for lung diseases. They covered results of human trials, the hurdles facing gene-transfer methods, newer delivery vehicles called vectors, and possible strategies for lung cancer, asthma, pulmonary fibrosis and acute lung injury. The article did not discuss asbestos. Citing a published listing, the authors reported that as of April 2000, 368 human gene therapy protocols had been approved in the U.S. At least 36 of these targeted lung diseases, two of them malignant mesothelioma. Elsewhere they wrote that four mesothelioma protocols had been approved in the U.S. and Europe. Describing earlier phase I trials, they wrote that injecting an adenovirus carrying a 'suicide gene' (HSVtk) into the chest was safe but caused strong immune responses. Because phase II results had not been reported, they said the effectiveness against mesothelioma of the HSVtk gene combined with the drug ganciclovir had not been established. The authors concluded that human gene therapy protocols had so far had limited success in showing benefit over conventional therapies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published gene therapy research and clinical protocols for lung diseases (no new data collected)
• Who was studied: Published laboratory, animal and human gene therapy studies, and approved clinical protocols. The authors cite that as of April 2000, 368 human gene therapy protocols had been approved in the U.S. At least 36 of these targeted lung diseases: 23 for cystic fibrosis, 10 for small cell or non-small cell lung cancer, and two for malignant mesothelioma.
• Exposure: Not applicable. The review concerns gene-transfer vectors (adenovirus, cationic liposomes, adeno-associated virus, lentivirus and others), not asbestos or any other exposure.
• Main results:
  • Malignant mesothelioma (described in the article as 'of the lung'): the authors wrote that a total of four clinical protocols had been approved in the U.S. and Europe.
  • Mesothelioma, as reported from earlier studies: phase I trials found that direct injection into the chest of an adenovirus carrying the HSVtk gene was safe. However, it caused strong immune responses against the vector and the gene product.
  • Mesothelioma: because phase II results had not been reported, the effectiveness of the HSVtk gene plus ganciclovir (GCV) prodrug strategy had not been established.
  • Lung cancer, from earlier p53 gene trials: regardless of the vector used, approximately 30% of treated patients showed a reduction in tumor size, and another 30% showed stabilization.
  • Cystic fibrosis, from earlier trials: gene transfer to the airway was relatively safe, but at the time it was not sufficient to produce therapeutic effects in humans.
• The authors' conclusion: The authors concluded that current human gene therapy protocols had shown only limited success in demonstrating benefit over conventional therapies. They also said the concept of using genes as drugs had been shown to be feasible and that vector systems were evolving rapidly.

Topics

Medical terms in this study, explained in our Lexicon: Fibrosis, Carcinoma, Lung Cancer, Pulmonary Fibrosis.

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