Journal article
Lentivirus Vector Can Be Readministered to Nasal Epithelia without Blocking Immune Responses
Journal of virology, Vol.82(21), pp.10684-10692
11/2008
DOI: 10.1128/JVI.00227-08
PMCID: PMC2573216
PMID: 18768988
Abstract
For many envisioned applications of lentivirus vectors as tools in respiratory biology and therapeutic gene delivery, the efficiency of gene transfer must be improved. We previously demonstrated stable, persistent (>11 months) in vivo expression following a single application of a feline immunodeficiency virus (FIV)-based lentivirus vector (GP64-FIV) to murine nasal epithelia. Here we investigate the efficacy of repeated administration of lentivirus vectors to the airways. Using quantitative bioluminescent imaging, we found that consecutive daily dosing achieved a linear increase in gene expression and greatly increased the number of epithelial cells targeted. Surprisingly, reporter gene expression also increased additively following each of seven doses of FIV delivered over consecutive weeks (1 dose/week), without the development of systemic or local neutralizing antibodies. This approach enhanced expression of both reporter and therapeutic transgenes. Transduction efficiency achieved following a single dose of FIV expressing mouse erythropoietin was insufficient to increase hematocrit, whereas seven consecutive daily doses significantly increased hematocrit. These unexpected results contrast strikingly with findings reported for adenovirus vectors. Prolonged gene expression has been observed in vivo following a single dose of virus vector; however, depending on the application, repeated administration of vector may be necessary to achieve stable, therapeutic gene expression.
Details
- Title: Subtitle
- Lentivirus Vector Can Be Readministered to Nasal Epithelia without Blocking Immune Responses
- Creators
- Patrick L Sinn - Program in Gene Therapy, Carver College of Medicine Department of PediatricsAriadna C Arias - Program in Gene Therapy, Carver College of Medicine Department of PediatricsKim A Brogden - Program in Gene Therapy, Carver College of Medicine Department of PediatricsPaul B McCray - Program in Gene Therapy, Carver College of Medicine Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.82(21), pp.10684-10692
- DOI
- 10.1128/JVI.00227-08
- PMID
- 18768988
- PMCID
- PMC2573216
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology (ASM)
- Language
- English
- Date published
- 11/2008
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Periodontics; Internal Medicine
- Record Identifier
- 9984093362102771
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