Journal article
Minimum Requirements for Efficient Transduction of Dividing and Nondividing Cells by Feline Immunodeficiency Virus Vectors
Journal of virology, Vol.73(6), pp.4991-5000
06/1999
DOI: 10.1128/JVI.73.6.4991-5000.1999
PMCID: PMC112543
PMID: 10233961
Abstract
The development of gene delivery vectors based on feline immunodeficiency virus (FIV) is an attractive alternative to vectors based on primate sources for the delivery of genes into humans. To investigate the requirements for efficient transduction of dividing and nondividing cells by vector particles based on FIV, a series of packaging and vector constructs was generated for which viral gene expression was minimized and from which unnecessary
cis
-acting sequences were deleted. Pseudotyped vector particles produced in 293T cells were used to transduce various target cells, including contact-inhibited human skin fibroblasts and growth-arrested HT1080 cells. FIV vectors in which the U3 promoter was replaced with the cytomegalovirus promoter gave rise to over 50-fold-higher titers than FIV vectors containing the complete FIV 5′ long terminal repeat (LTR). Comparison of the transduction efficiencies of vectors containing different portions of the FIV Gag coding region indicates that at least a functional part of the FIV packaging signal (Ψ) is located within an area which includes the 5′ LTR and the first 350 bp of
gag
. Transduction efficiencies of vectors prepared without FIV
vif
and
orf2
accessory gene expression did not differ substantially from those of vectors prepared with accessory gene expression in either dividing or nondividing cells. The requirement for FIV
rev
-RRE was, however, demonstrated by the inefficient production of vector particles in the absence of
rev
expression. Together, these results demonstrate the efficient transduction of nondividing cells in vitro by a multiply attenuated FIV vector and contribute to an understanding of the minimum requirements for efficient vector production and infectivity. In addition, we describe the ability of an FIV vector to deliver genes in vivo into hamster muscle tissue.
Details
- Title: Subtitle
- Minimum Requirements for Efficient Transduction of Dividing and Nondividing Cells by Feline Immunodeficiency Virus Vectors
- Creators
- Julie C Johnston - Center for Gene Therapy, Chiron Technologies, San Diego, California 92121Mehdi Gasmi - Center for Gene Therapy, Chiron Technologies, San Diego, California 92121Leland E Lim - Center for Gene Therapy, Chiron Technologies, San Diego, California 92121John H Elder - Center for Gene Therapy, Chiron Technologies, San Diego, California 92121Jiing-Kuan Yee - Center for Gene Therapy, Chiron Technologies, San Diego, California 92121Douglas J Jolly - Center for Gene Therapy, Chiron Technologies, San Diego, California 92121Kevin P Campbell - Center for Gene Therapy, Chiron Technologies, San Diego, California 92121Beverly L Davidson - Center for Gene Therapy, Chiron Technologies, San Diego, California 92121Sybille L Sauter - Center for Gene Therapy, Chiron Technologies, San Diego, California 92121
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.73(6), pp.4991-5000
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/JVI.73.6.4991-5000.1999
- PMID
- 10233961
- PMCID
- PMC112543
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Language
- English
- Date published
- 06/1999
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068389802771
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