Gene transfer to adult human lung tissue ex vivo.

Abstract:

:The potential of gene therapy for treatment of lung disease remains unrealised. Early model systems often resulted in promising efficiency of gene transfer, only to prove irreproducible in the clinic. While problems such as induction of host immune responses and duration of expression also need to be addressed, it is now widely believed that alternative, relevant models which more accurately reflect gene transfer efficiencies in human lungs are urgently required. We report here on a human lung slice culture system to assess gene transfer to adult lung epithelium. A lacZ-expressing adenovirus (AdCA35lacZ) was used as a reporter vector. A solution of AdCA35lacZ was instilled via bronchioles into resected lung tissue, a route analogous to clinical administration. Following a 1 h incubation, the tissue was inflated with a 0.4% agarose solution, instilled via the same bronchioles. Once solidified, 500 microm slices of the tissue were prepared and cultured for 4 days. beta-Galactosidase staining revealed lacZ transgene expression in bronchiolar and alveolar cells of the lung slices throughout the 4 days in culture. This system, which can also be used to study other viral and liposome vectors, could prove to be a useful alternative model for assessing gene delivery to adult human lung epithelium.

journal_name

Gene Ther

journal_title

Gene therapy

authors

McBride S,Rannie D,Harrison DJ

doi

10.1038/sj.gt.3301146

keywords:

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

675-8

issue

8

eissn

0969-7128

issn

1476-5462

journal_volume

7

pub_type

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