Enhanced gene expression in mouse lung after PEI-DNA aerosol delivery
Aerosol gene delivery to the pulmonary system has vast potential for many diseases, including cystic fibrosis and lung cancer. We recently reported that polyethyleneimine (PEI), a cationic polymer, holds promise as a gene delivery vector for transfection in lung by aerosol. To further optimize the gene expression in the lung by aerosol, we utilized 5% CO(2) in air for the nebulization of PEI-DNA complexes. Five percent CO(2)-in-air gave a threefold higher gene expression compared to normal air using the chloramphenicol acetyl transferase (CAT) reporter gene delivered by Aerotech II nebulizer. The delivery of DNA by PEI was dose dependent with the highest expression obtained when 2 mg of DNA in 10 ml was nebulized at a PEI nitrogen:DNA phosphate (N:P) ratio of 10:1. The optimal N:P ratio for lung transfection was found to be between 10:1 and 20:1 using the CAT and luciferase reporter genes. The time-course studies showed the highest expression at 24 h after aerosol delivery and 40-50% of peak level was detectable even after a week. Tissue distribution indicates the expression to be specific to the lung with no detectable expression in any other tissue examined. Histological and biochemical analysis of lungs revealed no evidence of acute inflammation.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2000 |
|---|---|
| Erschienen: |
2000 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:2 |
|---|---|
| Enthalten in: |
Molecular therapy : the journal of the American Society of Gene Therapy - 2(2000), 1 vom: 29. Juli, Seite 63-70 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gautam, A [VerfasserIn] |
|---|
| Anmerkungen: |
Date Completed 21.09.2000 Date Revised 21.11.2013 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM108239497 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM108239497 | ||
| 003 | DE-627 | ||
| 005 | 20231222144738.0 | ||
| 007 | tu | ||
| 008 | 231222s2000 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0361.xml |
| 035 | |a (DE-627)NLM108239497 | ||
| 035 | |a (NLM)10899829 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gautam, A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Enhanced gene expression in mouse lung after PEI-DNA aerosol delivery |
| 264 | 1 | |c 2000 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 21.09.2000 | ||
| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aerosol gene delivery to the pulmonary system has vast potential for many diseases, including cystic fibrosis and lung cancer. We recently reported that polyethyleneimine (PEI), a cationic polymer, holds promise as a gene delivery vector for transfection in lung by aerosol. To further optimize the gene expression in the lung by aerosol, we utilized 5% CO(2) in air for the nebulization of PEI-DNA complexes. Five percent CO(2)-in-air gave a threefold higher gene expression compared to normal air using the chloramphenicol acetyl transferase (CAT) reporter gene delivered by Aerotech II nebulizer. The delivery of DNA by PEI was dose dependent with the highest expression obtained when 2 mg of DNA in 10 ml was nebulized at a PEI nitrogen:DNA phosphate (N:P) ratio of 10:1. The optimal N:P ratio for lung transfection was found to be between 10:1 and 20:1 using the CAT and luciferase reporter genes. The time-course studies showed the highest expression at 24 h after aerosol delivery and 40-50% of peak level was detectable even after a week. Tissue distribution indicates the expression to be specific to the lung with no detectable expression in any other tissue examined. Histological and biochemical analysis of lungs revealed no evidence of acute inflammation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Aerosols |2 NLM | |
| 650 | 7 | |a Carbon Dioxide |2 NLM | |
| 650 | 7 | |a 142M471B3J |2 NLM | |
| 650 | 7 | |a Polyethyleneimine |2 NLM | |
| 650 | 7 | |a 9002-98-6 |2 NLM | |
| 650 | 7 | |a DNA |2 NLM | |
| 650 | 7 | |a 9007-49-2 |2 NLM | |
| 650 | 7 | |a Peroxidase |2 NLM | |
| 650 | 7 | |a EC 1.11.1.7 |2 NLM | |
| 650 | 7 | |a Luciferases |2 NLM | |
| 650 | 7 | |a EC 1.13.12.- |2 NLM | |
| 650 | 7 | |a Chloramphenicol O-Acetyltransferase |2 NLM | |
| 650 | 7 | |a EC 2.3.1.28 |2 NLM | |
| 700 | 1 | |a Densmore, C L |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, B |e verfasserin |4 aut | |
| 700 | 1 | |a Waldrep, J C |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular therapy : the journal of the American Society of Gene Therapy |d 2000 |g 2(2000), 1 vom: 29. Juli, Seite 63-70 |w (DE-627)NLM108239381 |x 1525-0024 |7 nnns |
| 773 | 1 | 8 | |g volume:2 |g year:2000 |g number:1 |g day:29 |g month:07 |g pages:63-70 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 2 |j 2000 |e 1 |b 29 |c 07 |h 63-70 | ||