2 CF Articles..one on Cepacia

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" Bronchial Artery Delivery of Viral Vectors for Gene delivery in Cystic

Fibrosis; Superior to Airway Delivery? "

Ameet Bakhai Dr, MRCP1, 2 , Desmond J Sheridan Professor, FRCP3 and

C Coutelle Professor, Dr.sc.med4

1Clinical Trials & Evaluation Unit, Royal Brompton & Harefield NHS Trust,

Britten Wing, Sydney Street, SW3 6NP, London U.K

2Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA

02115, USA. a.bakhai@...

3Academic Cardiology Unit, Division of National Heart and Lung Institute,

Imperial College Faculty of Medicine at St 's Hospital, Praed Street,

W2 1NY, London U.K. d.sheridan@...

4Gene Therapy Research Group, Division of Biomedical Sciences, Imperial

College School of Science, Technology and Medicine, Sir Fleming

Building, Exhibition road, SW7 2AZ, London U.K. c.coutelle@...

BMC Pulmonary Medicine 2002 2: 2

Abstract

Background

Attempts at gene therapy for the pulmonary manifestations of

Cystic Fibrosis have relied mainly on airway delivery. However the

efficiency of gene transfer and expression in the airway epithelia has

not reached therapeutic levels. Access to epithelial cells is not

homogenous for a number of reasons and the submucosal glands cannot be

reached via the airways.PresentationWe propose to inject gene delivery

vectors directly into bronchial arteries combined with pre-delivery of

vascular endothelial growth factor to increase vascular endothelial

permeability and post-delivery flow reduction by balloon occlusion. Thus

it may be possible to reach mucous secreting cells of the bronchial

luminal epithelium and the submucosal glands in an increased and

homogenous fashion.TestingThis combination of techniques to the best of

our knowledge has not previously been investigated, and may enable us to

overcome some of the current limitations to gene therapy for Cystic

Fibrosis.

Binding of protegrin-1 to Pseudomonas aeruginosa and Burkholderia cepacia

Mark T Albrecht1  Wei Wang2  Olga Shamova2 I Lehrer2, 3 and Neal L

Schiller1

1Division of Biomedical Sciences, University of California, Riverside,

California 92521, USA.

2Department of Medicine, University of California, Los Angeles, Los

Angeles, California 90095, USA.

3Molecular Biology Institute, University of California, Los Angeles, Los

Angeles, California 90095, USA.

Respir Res 2002 3: 18

Abstract

Background

Pseudomonas aeruginosa and Burkholderia cepacia infections of

cystic fibrosis patients' lungs are often resistant to conventional

antibiotic therapy. Protegrins are antimicrobial peptides with potent

activity against many bacteria, including P. aeruginosa. The present

study evaluates the correlation between protegrin-1 (PG-1)

sensitivity/resistance and protegrin binding in P. aeruginosa and B.

cepacia.MethodsThe PG-1 sensitivity/resistance and PG-1 binding

properties of P. aeruginosa and B. cepacia were assessed using radial

diffusion assays, radioiodinated PG-1, and surface plasmon resonance

(BiaCore).ResultsThe six P. aeruginosa strains examined were very

sensitive to PG-1, exhibiting minimal active concentrations from

0.0625–0.5 µg/ml in radial diffusion assays. In contrast, all five B.

cepacia strains examined were greater than 10-fold to 100-fold more

resistant, with minimal active concentrations ranging from 6–10 µg/ml.

When incubated with a radioiodinated variant of PG-1, a sensitive P.

aeruginosa strain bound considerably more protegrin molecules per cell

than a resistant B. cepacia strain. Binding/diffusion and surface plasmon

resonance assays revealed that isolated lipopolysaccharide (LPS) and

lipid A from the sensitive P. aeruginosa strains bound PG-1 more

effectively than LPS and lipid A from resistant B. cepacia

strains.ConclusionThese findings support the hypothesis that the relative

resistance of B. cepacia to protegrin is due to a reduced number of PG-1

binding sites on the lipid A moiety of its LPS.

Becki

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