Electronic Journal of Biotechnology ISSN: 0717-3458 |
Vol.
12 No. 4, Issue of October 15, 2009 |
© 2009 by Pontificia Universidad Católica
de Valparaíso -- Chile |
Received August 6, 2008
/ Accepted June 1, 2009 |
DOI: 10.2225/vol12-issue4-fulltext-5 |
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Can painting human
cells with exogenous maltoporin enable efficient therapeutic gene
transfer by bacteriophage lambda vectors?
Oleg Tolmachov
National Heart and Lung Institute
Imperial College London
Sir Alexander Fleming Building,
Exhibition Road
London, United Kingdom
E-mail o.tolmachov@imperial.ac.uk
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.
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