Non-viral approaches to gene therapy

Cotten, Matthew; Wagner, Ernst

doi:10.1016/0958-1669(93)90053-y

Cited by 126 publications

(46 citation statements)

References 37 publications

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“…Specifically, it has been shown that cationic liposomes are clinically well tolerated, easy to produce, noninfectious, nonimmunogenic, and able to transfect slowly dividing cells. 3,4 Receptor-mediated gene delivery can potentially improve efficiency and safety further by selectively targeting a cell population expressing the surface receptor for a ligand. The efficiency of gene transfer by receptor-mediated endocytosis of polycation -DNA complexes has been enhanced by the incorporation of endosomolytic agents, such as adenoviral capsids or fusogenic peptides.…”

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confidence: 99%

Effective gene transfer to solid tumors using different nonviral gene delivery techniques: Electroporation, liposomes, and integrin-targeted vector

et al. 2002

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In this study, we measured transfection efficiency in vitro and in vivo using the following nonviral approaches of gene delivery: injection of plasmid DNA, electroporation -assisted, liposome -enhanced, and integrin -targeted gene delivery, as well as the combination of these methods. Four histologically different tumor models were transfected with a plasmid encoding the green fluorescent protein ( GFP ) ( B16 mouse melanoma, P22 rat carcinosarcoma, SaF mouse sarcoma, and T24 human bladder carcinoma ) using adherent cells, dense cell suspensions, and solid tumors. Emphasis was placed on different electroporation conditions to optimise the duration and amplitude of the electric pulses, as well as on different DNA concentrations for effective gene delivery. In addition, transfection efficiency was correlated with cell density of the tumors. The major in vivo findings were: ( a ) electroporationassisted gene delivery with plasmid DNA, employing long electric pulses with low amplitude, yielded significantly better GFP expression than short electric pulses with high amplitude; ( b ) electroporation combined with liposome -DNA complexes yielded the highest percentage of transfected tumor area in B16F1 tumor ( 6% ); ( c ) transfection efficiency of electroporation -assisted plasmid DNA delivery was dependent on tumor type; ( d ) integrin -targeted vector, alone or combined with electroporation, was largely ineffective. In conclusion, our results demonstrate that some nonviral methods of gene delivery are feasible and efficient in transfecting solid tumors. Therefore, this makes nonviral methods attractive for further development.

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confidence: 99%

Effective gene transfer to solid tumors using different nonviral gene delivery techniques: Electroporation, liposomes, and integrin-targeted vector

et al. 2002

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“…12 Cavifor the uptake of plasmid DNA into mammalian cells tation is well known as a powerful mechanism of tissue have been developed in the past, including coprecipidamage induction based on severe ultrastructural altertation with calcium phosphate, 1 use of polycations or lipations at the cellular and subcellular level. 13 Whereas a ids to form complexes with DNA, 2 encapsidation of plasdefined portion of shock wave-exposed cells is commid DNA into liposomes or erythrocyte ghosts, [3][4][5] pletely destroyed and reduced to cell debris (dependent exposure of cells to rapid pulses of high-voltage current, upon the applied number of discharges and their pulse ie electroporation, 6,7 receptor-mediated endocytosis of energy), the majority of cells surviving the shock wave-DNA-ligand complexes 8 and introduction of DNA into exposure procedure has been shown to continue to procells by direct microinjection 9 or on high-velocity tungliferate at a near normal rate. 14 Interestingly, different cell sten microprojectiles.…”

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confidence: 99%

“…20 Thus, the disadvantageous usage of the endosopropagation wave was focused to the second focus of the ellipsoid where a 2.5 ml silicone-stopper sealed polymal pathway, which is employed in receptor-mediated gene transfer, is omitted. 8 (4) The ineffectiveness of plaspropylene vial (Nunc, Wiesbaden, Germany) containing the respective suspended cells was positioned without mid DNA transfer across the nuclear membrane -limiting expression efficiency of successfully transferred, cytoany residual air in the vial. The position of the second focus was indicated by the intersection of two positioning plasmically localized nucleic acids -can be overcome potentially by utilization of nucleus-independent laser beams ( Figure 1).…”

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Shock wave permeabilization as a new gene transfer method

Lauer

Bürgelt

Squire³

et al. 1997

Gene Ther

136

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Uptake of naked functional DNA into mammalian cells can eukaryotic cells display a temporary increase in membrane be achieved by a number of physical methods. However, permeability. This effect was shown to be caused by cavifor most of these techniques possibilities for therapeutic in tation resulting in the transient generation of cell pores vivo applications -especially to solid organs -are often which allows the direct transfer of naked plasmid DNA. limited. In this report, we describe shock wave permeabilizShockwave transfection of a variety of cell lines was demation as a new physical gene transfer method, which can onstrated. Since shock waves can be well focused within be easily applied, provides great flexibility in the size and particular body regions, future applications of extracorporsequence of the DNA molecules to be delivered, and which ally generated shock waves to tissues simultaneously pershould exhibit an advantageous security profile in vivo.fused with DNA solutions might open up the possibility of Upon exposure to lithotripter-generated shock waves achieving a regionally enhanced in vivo gene transfer.

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“…4 -7,26 A variety of liposomes and polymers have been developed and shown in recent years to be highly effective in gene transfer; however, most of these agents are nonspecific. 3,27,28 Targeting of nonviral gene delivery has been achieved by incorporating into the vectors ligands that can specifically recognize surface markers of the cells. Notably, transferrin incorporated into liposomes can substantially enhance efficiency of gene transfer mediated by the liposome.…”

Section: Discussionmentioning

confidence: 99%

Single-chain antibody-mediated gene delivery into ErbB2-positive human breast cancer cells

Stuckert

Bosch

et al. 2001

Cancer Gene Ther

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Targeted gene transfer by nonviral vectors can be achieved through incorporation of specific ligand( s ) into the vectors. In this study, the effects of incorporation of an anti -ErbB2 single -chain antibody fragment ( ScFv ) into nonviral vectors for targeted gene delivery were investigated. The ML39 ScFv, selected from a human ScFv phage display library and affinity matured in vitro ( K d =1Â10 À 9 M ), was used as ligand specific for the extracellular domain of the tumor surface protein, ErbB2. Two approaches were taken: ( a ) development of a vector that is composed of a bifunctional fusion protein capable of binding DNA with the ErbB2 -specific ML39 ScFv at its N -terminus and a truncated form of human protamine at its C -terminus, and ( b ) formulation and evaluation of delivery vectors consisting of three independent components including ML39 ScFv, protamine, and cationic lipids. We demonstrate that fusion proteins comprised of the ML39 ScFv and a truncated form of protamine, denoted as ScFv -P -S, can selectively deliver exogenous DNA into ErbB2( + ) cells, with an 8 -to 10 -fold increase in expression levels of the luciferase reporter gene in ErbB2( + ) cells as compared to ErbB2( À ) cells. In addition, vectors formulated by appropriately mixing DNA, ScFv, protamine, and lipids in vitro could even more efficiently deliver the reporter gene into ErbB2( + ) cells with approximately 5 -fold increase in gene expression in ErbB2( + ) cell as compared to ErbB2( À ) cells. Expression and refolding of the ScFv fusion proteins, in addition to determination of optimal conditions for vector development using these approaches, are discussed.

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Non-viral approaches to gene therapy

Cited by 126 publications

References 37 publications

Effective gene transfer to solid tumors using different nonviral gene delivery techniques: Electroporation, liposomes, and integrin-targeted vector

Effective gene transfer to solid tumors using different nonviral gene delivery techniques: Electroporation, liposomes, and integrin-targeted vector

Shock wave permeabilization as a new gene transfer method

Single-chain antibody-mediated gene delivery into ErbB2-positive human breast cancer cells

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