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Link to original content: https://pubmed.ncbi.nlm.nih.gov/17700544/
Stable gene transfer to muscle using non-integrating lentiviral vectors - PubMed Skip to main page content
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. 2007 Nov;15(11):1947-54.
doi: 10.1038/sj.mt.6300281. Epub 2007 Aug 14.

Stable gene transfer to muscle using non-integrating lentiviral vectors

Luis Apolonia  1 , Simon N Waddington, Carolina Fernandes, Natalie J Ward, Gerben Bouma, Michael P Blundell, Adrian J Thrasher, Mary K Collins, Nicola J Philpott
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Free article

Stable gene transfer to muscle using non-integrating lentiviral vectors

Luis Apolonia et al. Mol Ther. 2007 Nov.
Free article

Abstract

Human immunodeficiency virus (HIV)-based lentiviral vectors (LVs) hold immense promise for gene delivery applications because of their relatively large packaging capacity and their ability to infect a range of cell types. The genome of HIV non-specifically integrates into the host genome, and this promotes efficient, stable transgene expression in dividing cells. However, integration can also be problematic because of variations in gene expression among cells, possible gene silencing and, most importantly, insertional mutagenesis which can lead to undesirable effects such as malignant transformation. In order to alleviate these problems, we have developed a range of non-integrating LVs (NILVs) by introducing point mutations into the catalytic site, chromosome binding site, and viral DNA binding site of the viral integrase (IN). In addition, we have mutated the IN attachment (att) sites within the HIV long terminal repeats (LTRs). All of the vectors produced show efficient reverse transcription and transgene expression in dividing cells and prolonged expression in non-dividing myotubes. Finally, we show that NILV can be used for achieving highly effective gene transfer and expression in muscle in vivo.

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