Virus gene transfer

Garrett, D. et al.. In utero recombinant adeno-associated virus gene transfer in mice, rats, and primates, BMC Biotech., 3,16,2003. 

Viruses are infectious particles formed by nucleic acid, proteins, and in some cases lipids. As viruses (for example, retro- and adenoviruses) transfer viral genes into cells with high efficiency, modified forms are sometimes used as vectors for gene transfer. However, procedures using virus-based vectors are often significantly more complicated and time-consuming than other transfection methods. In addition, viral vectors are potentially hazardous, and biological safety issues need to be considered carefully. Therefore, techniques that combine... 

Membrane translocating peptides are promising vehicles for the transfer of macromolecules into the tissues. Recent report of Schwarze et al. [249] demonstrated that a signal peptide from Hl-virus could transfer betagalactosidase protein to virtually all tissues in rat after intravenous and intraperitoneal injections. In the case of proteins, folding phenomena affect their membrane translocation and these features may be different for gene-based drugs. 

Several enveloped viruses, and some physical gene transfer techniques such as electroporation, deliver the nucleic acid into the cell by direct crossing of the cell membrane. Lipid-based, enveloped systems can do this by a physiological, selfsealing membrane fusion process, avoiding physical damage of the cell membrane. For cationic lipid-mediated delivery of siRNA, most material is taken up by endo-cytotic processes. Recently, direct transfer into the cytosol has been demonstrated to be the bioactive delivery principle for certain siRNA lipid formulations [151]. 

ErbacherP, Remy JS, Behr JP (1999) Gene transfer with synthetic virus-like particles via the integrin-mediated endocytosis pathway. Gene Ther 6 138-145... 

Plank C, Oberhauser B, Mechtler K, Koch C, Wagner E (1994) The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer systems. J Biol Chem 269 12918-12924... 

Wagner E (2004) Strategies to improve DNA polyplexes for in vivo gene transfer will artificial viruses be the answer Pharm Res 21 8-14... 

Lee, J.H., Baker, T.J., Mahal, L.K., Zabner, J., Bertozzi, C.R., Wiemer, D.F., and Welsh, M.J. (1999) Engineering novel cell surface receptors for virus-mediated gene transfer./. Biol. Chem. 274, 21878. 

Integration is random, mostly on dividing cells Transient fnnction of genes Small capacity for foreign genes Less efficient than viruses Inefficient gene transfer... 

Pitard B, et al. Virus-sized self-assembling lamellar complexes between plasmid DNA and cationic micelles promote gene transfer. Proc Natl Acad Sci USA 1997 94 14412. 

Wagner E, Plank C, Zatloukal K, et al. Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes toward a synthetic virus-like gene-transfer vehicle. Proc Natl Acad Sci USA 1992 89(17) 7934-7938. 

Viruses Shunt that prevents transfer of organic carbon and nutrients to higher trophic levels Infects prokaryotes and eukaryotes sometimes very specific to host. Thought to be responsible for lateral gene transfer... 

Answer Aerosol delivery of the CFTR gene. Both viruses and liposome-DNA complexes are capable of successful CFTR gene transfer to the nasal and airway epithelia of patients with CF. In fact, gene transfer to the airways is one of the few areas where liposome-DNA complexes match the expression obtained using viral vectors without the viruses inflammatory side effects. Current trials are aimed at optimizing gene delivery with reduced toxicity to produce sustained correction of the epithelial transport defect. 

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