Abstract:
:Gene therapy, i.e., the expression in cells of genetic material with therapeutic activity, holds great promise for the treatment of human diseases. A delivery vehicle (vector), of either viral or non-viral origin, must be used to carry the foreign gene into a cell. Viral vectors take advantage of the facile integration of the gene of interest into the host and high probability of its long-term expression but are plagued by safety concerns. Non-viral vectors, although less efficient at introducing and maintaining foreign gene expression, have the profound advantage of being non-pathogenic and non-immunogenic; they are the subject of this review. Polycation-DNA complexes are particularly attractive for non-viral gene therapy. To perform, they have to attach to the target cell surface, be internalized, escape from endosomes, find a way to the nucleus, and, finally, be available for transcription. The clinical usefulness of polycationic vectors depends on elucidating the role each of these steps plays in gene transfer. Recent progress in consequent rational vector improvement is highlighted by our finding of polyethylenimine derivatives more potent and yet less cytotoxic than the 25-kDa polyethylenimine (one of the most effective non-viral vectors). Such vectors could be further modified with cell-targeting ligands to enhance their utility for in vivo applications.
journal_name
Appl Microbiol Biotechnoljournal_title
Applied microbiology and biotechnologyauthors
Thomas M,Klibanov AMdoi
10.1007/s00253-003-1321-8subject
Has Abstractpub_date
2003-07-01 00:00:00pages
27-34issue
1eissn
0175-7598issn
1432-0614journal_volume
62pub_type
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