Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes

D. Goula, N. Becker, G. F. Lemkine, P. Normandie, J. Rodrigues, S. Mantero, G. Levi, B. A. Demeneix

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Intravenous administration could become a delivery route of choice for prophylactic and curative gene therapies on condition that genes cross the capillary barrier and reach target tissues without being degraded. We investigated the kinetics and process of transgene delivery through mouse lung capillaries following DNA complexation with linear polyethylenimine (L-PEI) and intravenous injection. Using digoxin-labeled DNA we followed the cellular localization of DNA at different times after injection and correlated these findings with cell markers and transgene expression. At 2 h after injection some DNA was still localized on the interior of the capillary lumen, but other complexes had already crossed the barrier and resulted in gene expression. At 24 h after injection most labeled DNA was localised in pulmonary cells, as was transgene expression. Only rarely was transgene expression found in endothelial cells, suggesting that the complexes cross the capillary barrier rapidly. Levels of caspase-1-like activity did not increase following transfection implying that L-PEI/DNA complexes are transported across cellular barriers by a non-damaging, physiological process, without causing inflammation. The high levels of expression of different transgenes in pneumocytes indicates that transport of L-PEI/DNA complexes through the endothelial barrier does not affect their transfection capacity. These findings open up new possibilities for gene delivery and its application to the lung.

Original languageEnglish
Pages (from-to)499-504
Number of pages6
JournalGene Therapy
Volume7
Issue number6
Publication statusPublished - Mar 2000

Fingerprint

Polyethyleneimine
Transgenes
Lung
DNA
Injections
Transfection
Physiological Phenomena
Alveolar Epithelial Cells
Caspase 1
Digoxin
Intravenous Injections
Intravenous Administration
Genetic Therapy
Genes
Endothelial Cells
Inflammation
Gene Expression

Keywords

  • Apoptosis
  • Cationic polymers
  • In vivo gene transfer
  • Lung
  • Synthetic vectors

ASJC Scopus subject areas

  • Genetics

Cite this

Goula, D., Becker, N., Lemkine, G. F., Normandie, P., Rodrigues, J., Mantero, S., ... Demeneix, B. A. (2000). Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes. Gene Therapy, 7(6), 499-504.

Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes. / Goula, D.; Becker, N.; Lemkine, G. F.; Normandie, P.; Rodrigues, J.; Mantero, S.; Levi, G.; Demeneix, B. A.

In: Gene Therapy, Vol. 7, No. 6, 03.2000, p. 499-504.

Research output: Contribution to journalArticle

Goula, D, Becker, N, Lemkine, GF, Normandie, P, Rodrigues, J, Mantero, S, Levi, G & Demeneix, BA 2000, 'Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes', Gene Therapy, vol. 7, no. 6, pp. 499-504.
Goula D, Becker N, Lemkine GF, Normandie P, Rodrigues J, Mantero S et al. Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes. Gene Therapy. 2000 Mar;7(6):499-504.
Goula, D. ; Becker, N. ; Lemkine, G. F. ; Normandie, P. ; Rodrigues, J. ; Mantero, S. ; Levi, G. ; Demeneix, B. A. / Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes. In: Gene Therapy. 2000 ; Vol. 7, No. 6. pp. 499-504.
@article{75675fd0b57d4ff39a0bfbad87757e7f,
title = "Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes",
abstract = "Intravenous administration could become a delivery route of choice for prophylactic and curative gene therapies on condition that genes cross the capillary barrier and reach target tissues without being degraded. We investigated the kinetics and process of transgene delivery through mouse lung capillaries following DNA complexation with linear polyethylenimine (L-PEI) and intravenous injection. Using digoxin-labeled DNA we followed the cellular localization of DNA at different times after injection and correlated these findings with cell markers and transgene expression. At 2 h after injection some DNA was still localized on the interior of the capillary lumen, but other complexes had already crossed the barrier and resulted in gene expression. At 24 h after injection most labeled DNA was localised in pulmonary cells, as was transgene expression. Only rarely was transgene expression found in endothelial cells, suggesting that the complexes cross the capillary barrier rapidly. Levels of caspase-1-like activity did not increase following transfection implying that L-PEI/DNA complexes are transported across cellular barriers by a non-damaging, physiological process, without causing inflammation. The high levels of expression of different transgenes in pneumocytes indicates that transport of L-PEI/DNA complexes through the endothelial barrier does not affect their transfection capacity. These findings open up new possibilities for gene delivery and its application to the lung.",
keywords = "Apoptosis, Cationic polymers, In vivo gene transfer, Lung, Synthetic vectors",
author = "D. Goula and N. Becker and Lemkine, {G. F.} and P. Normandie and J. Rodrigues and S. Mantero and G. Levi and Demeneix, {B. A.}",
year = "2000",
month = "3",
language = "English",
volume = "7",
pages = "499--504",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes

AU - Goula, D.

AU - Becker, N.

AU - Lemkine, G. F.

AU - Normandie, P.

AU - Rodrigues, J.

AU - Mantero, S.

AU - Levi, G.

AU - Demeneix, B. A.

PY - 2000/3

Y1 - 2000/3

N2 - Intravenous administration could become a delivery route of choice for prophylactic and curative gene therapies on condition that genes cross the capillary barrier and reach target tissues without being degraded. We investigated the kinetics and process of transgene delivery through mouse lung capillaries following DNA complexation with linear polyethylenimine (L-PEI) and intravenous injection. Using digoxin-labeled DNA we followed the cellular localization of DNA at different times after injection and correlated these findings with cell markers and transgene expression. At 2 h after injection some DNA was still localized on the interior of the capillary lumen, but other complexes had already crossed the barrier and resulted in gene expression. At 24 h after injection most labeled DNA was localised in pulmonary cells, as was transgene expression. Only rarely was transgene expression found in endothelial cells, suggesting that the complexes cross the capillary barrier rapidly. Levels of caspase-1-like activity did not increase following transfection implying that L-PEI/DNA complexes are transported across cellular barriers by a non-damaging, physiological process, without causing inflammation. The high levels of expression of different transgenes in pneumocytes indicates that transport of L-PEI/DNA complexes through the endothelial barrier does not affect their transfection capacity. These findings open up new possibilities for gene delivery and its application to the lung.

AB - Intravenous administration could become a delivery route of choice for prophylactic and curative gene therapies on condition that genes cross the capillary barrier and reach target tissues without being degraded. We investigated the kinetics and process of transgene delivery through mouse lung capillaries following DNA complexation with linear polyethylenimine (L-PEI) and intravenous injection. Using digoxin-labeled DNA we followed the cellular localization of DNA at different times after injection and correlated these findings with cell markers and transgene expression. At 2 h after injection some DNA was still localized on the interior of the capillary lumen, but other complexes had already crossed the barrier and resulted in gene expression. At 24 h after injection most labeled DNA was localised in pulmonary cells, as was transgene expression. Only rarely was transgene expression found in endothelial cells, suggesting that the complexes cross the capillary barrier rapidly. Levels of caspase-1-like activity did not increase following transfection implying that L-PEI/DNA complexes are transported across cellular barriers by a non-damaging, physiological process, without causing inflammation. The high levels of expression of different transgenes in pneumocytes indicates that transport of L-PEI/DNA complexes through the endothelial barrier does not affect their transfection capacity. These findings open up new possibilities for gene delivery and its application to the lung.

KW - Apoptosis

KW - Cationic polymers

KW - In vivo gene transfer

KW - Lung

KW - Synthetic vectors

UR - http://www.scopus.com/inward/record.url?scp=0034100728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034100728&partnerID=8YFLogxK

M3 - Article

C2 - 10757023

AN - SCOPUS:0034100728

VL - 7

SP - 499

EP - 504

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 6

ER -