Notable reduction in illegitimate integration mediated by a PPT-deleted, nonintegrating lentiviral vector

Journal Article (Journal Article)

Nonintegrating lentiviral vectors present a means of reducing the risk of insertional mutagenesis in nondividing cells and enabling short-term expression of potentially hazardous gene products. However, residual, integrase-independent integration raises a concern that may limit the usefulness of this system. Here we present a novel 3′ polypurine tract (PPT)-deleted lentiviral vector that demonstrates impaired integration efficiency and, when packaged into integrase-deficient particles, significantly reduced illegitimate integration. Cells transduced with PPT-deleted vectors exhibited predominantly 1-long terminal repeat (LTR) circles and a low level of linear genomes after reverse transcription (RT). Importantly, the PPT-deleted vector exhibited titers and in vitro and in vivo expression levels matching those of conventional nonintegrating lentiviral vectors. This safer nonintegrating lentiviral vector system will support emerging technologies, such as those based on transient expression of zinc-finger nucleases (ZFNs) for gene editing, as well as reprogramming factors for inducing pluripotency. © The American Society of Gene & Cell Therapy.

Full Text

Duke Authors

Cited Authors

  • Kantor, B; Bayer, M; Ma, H; Samulski, J; Li, C; McCown, T; Kafri, T

Published Date

  • January 1, 2011

Published In

Volume / Issue

  • 19 / 3

Start / End Page

  • 547 - 556

Electronic International Standard Serial Number (EISSN)

  • 1525-0024

International Standard Serial Number (ISSN)

  • 1525-0016

Digital Object Identifier (DOI)

  • 10.1038/mt.2010.277

Citation Source

  • Scopus