Can painting human cells with exogenous maltoporin enable efficient therapeutic gene transfer by bacteriophage lambda vectors?
File(s)5.pdf (40.26 KB)
Published version
Author(s)
Tolmachov, O
Type
Journal Article
Abstract
Many gene therapy strategies require transfer of high-molecular weight DNA into human cells. To enable clinical trials, these vectors need to be produced on a large scale and at low cost. The production of effective high-capacity vectors like HSV-amplicons and helper-dependent adenoviral vectors is difficult to up-scale, so new inexpensive vectors are needed for the efficient delivery of high-molecular weight DNA to human cells. Bacteriophage lambda vectors can accommodate up to about 46 kb of therapeutic DNA and can be easily produced in an industrial setting. However, the lambda vectors transfer DNA into mammalian cells with only a low efficiency. It was shown that bacteriophage lambda virions ejected their DNA in the presence of the purified receptor for bacteriophage lambda, maltoporin (LamB protein), encoded by the malB gene of Shigella sonnei 3070. This property of S. sonnei maltoporin was exploited for the bacteriophage injection-driven DNA loading of liposomes and other polymer nanocontainers displaying maltoporin. Relying on the above evidence I hypothesize that the efficient gene transfer by industrially produced bacteriophage lambda vector virions, such as cosmid transducing particles, to human cells can be accomplished after incorporation (protein painting) of the purified S. sonnei maltoporin into the human plasma membrane.
Version
Published version
Date Issued
2009
Citation
Electronic Journal of Biotechnology, 2009, 12(4)
ISSN
0717-3458
Publisher
Pontificia Universidad Católica de Valparaíso -- Chile
Journal / Book Title
Electronic Journal of Biotechnology
Volume
12(4)
Copyright Statement
© 2009 by Pontificia Universidad Católica de Valparaíso - Chile
Source Volume Number
12(4)
Subjects
gene therapy
LAMB
maltoporin
cell painting
bacteriophage vectors
Coverage Spatial
Chile
Article Number
5