Can painting human cells with exogenous maltoporin enable efficient therapeutic gene transfer by bacteriophage lambda vectors?

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.