Transfection polymers

Uchegbu and coworkers have studied the complexation and delivery of DNA using a unique poly(amino acid)-based polymer vesicle. A polymer of either poly (L-lysine) or poly(L-omithine) was functionalized with methoxy-poly(ethylene glycol) (mPEG) and hydrophobic palmitic acid chains to synthesize an amphiphilic triblock of either mPEG-6-poly(L-lysine)-6-palmitoyl or mPEG-Z>-poly(L-omithine)-6-palmitoyl. Vesicles formed from these polymers were complexed with DNA and showed improved transfection in vitro over poly(amino acid) complexed with DNA or DNA alone [82]. 

AV Kabanov, FC Szoka Jr, LW Seymour. In PF AV Kabanov, LW Seymour, eds. Interpoly-electrolyte Complexes for Gene Delivery Polymer Aspects of Transfection Activity. Chichester, UK Wiley, 1998, pp 197-218. 

Another important aspect of transfection agents, especially for nonviral systems, was the efficiency/toxicity ratio. The CLS described by Olbrich et al. [19] showed only moderate transfection efficiencies compared with the established polymers... 

Haensler, J., and Szoka Jr., F.C., Polyamidoamine cascade polymers mediate efficient transfection of cells in culture, Bioconjugate Chemistry, 1993, 4, 372-379. 

First clinical human gene therapy trials with polyplexes were performed using cancer vaccines based on autologous patient tumor cells. These were modified ex vivo with interleukin-2 pDNA. To obtain high level transfection rates of patient s primary tumor cells, Tf-PLL/pDNA polyplexes linked with inactivated endosomolytic adenovirus particles were applied [221]. Polymer-based in vivo human gene transfer studies were performed with PEGylated PLL polyplexes, delivering CFTR pDNA to the airway epithelium of cystic fibrosis patients [222],... 

It should be emphasized at this point that the use of physicochemical methods is so far the only way to demonstrate the import of transgene DNA into the mitochondrial matrix in living mammalian cells. The unavailability of a mitochondria-specific reporter plasmid designed for mitochondrial expression severely hampers current efforts toward the development of effective mitochondrial expression vectors. Although any new nonviral transfection system (i.e., cationic lipids, polymers, and others) aimed at the nuclear-cytosolic expression of proteins can be systematically tested and subsequently improved by utilizing anyone of many commercially available reporter gene systems, such a methodical approach to develop mitochondrial transfection systems is currently impossible. 

Lynn DM, Anderson DG, Putnam D, Langer R (2001) Accelerated discovery of synthetic transfection vectors parallel synthesis and screening of a degradable polymer library. J Am Chem Soc 123 8155-8156... 

Transfection testing data for hyperbranched amidoamine polymers are provided in Table 1. 

Another cationic polymer, poly- -(4-aminobutyl)-L-glycolic) acid (PLAGA) has been shown to condense DNA efficiently and also to be less cytotoxic than PLL. PLAGA is biodegradable, not toxic to the cells, and enhances transfection in cultured cells (202). 

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