Gene delivery design

Benns JM, Kim SW (2000) Tailoring new gene delivery designs for specific targets. J Drug Target 8 1-12... 

Figure 20.1 Barriers to gene delivery - Design requirements for gene delivery systems include the ability to (a) package therapeutic genes (b) gain entry into cells (c) escape the endo-lysosomal pathway (d) effect DNA/vector release (e) traffic through the cytoplasm and into the nucleus (f) enable gene expression and remain biocompatible.

R. Martien, B. Loretz and A. B. Schnurch, Oral gene delivery design of polymeric carrier systems shielding toward intestinal enzymatic attack. Biopolymers, 83(4), 327-336 (2006). 

Pack DW, Hoffman AS, Pun S, Stayton PS (2005) Design and development of polymers for gene delivery. Nat Rev Drug Discov 4 581-593... 

Martin B, Sainlos M, Aissaoui A, Oudrhiri N, Hauchecome M, Vigneron JP, Lehn JM, Lehn P (2005) The design of cationic lipids for gene delivery. Curr Pharm Des 11 375-394... 

Kircheis, R., L. Wightman, and E. Wagner. 2001. Design and gene delivery activity of modified polyethylenimines. Adv Drug Deliv Rev 53(3) 341-58. 

Li S, Huang L. Functional polymorphism of liposomal gene delivery vectors lipoplex and lipopolyplex. In Janoff AS, ed. Liposomes Rational Design. New York Marcel Dekker, Inc., 1999 89. 

Leclercq F, et al. Design, S5mthesis and evaluation of gadolinium cationic lipids as tools for biodistribution studies of gene delivery complexes Bioconj Chem 2003 14 112. 

Leong KW (2006) Polymer design for nonviral gene delivery. BioMEMS Biomed Nanotech-nol 1 239-263... 

Pietersz GA, Tang C-K, Apostolopoulos V. Structure and design of polycationic carriers for gene delivery. Mini-Rev Med Chem 2006 6 1285-1298. 

The latter studies on pDNA delivery of a therapeutic gene to treat metabolic diseases, autoimmune diseases, viral infections or cancer suggest that naked pDNA could be used for gene delivery. The advantages of this type of therapy include the simplicity of i.m. injection, the requirement for only a limited number of i.m. injections to achieve measurable serum levels of the therapeutic protein, the maintenance of stable serum levels of the protein thereby avoiding side-effects associated with bolus protein delivery and the avoidance of the use of viral vectors which pose safety concerns and which can induce anti-vector antibodies. With improvements in pDNA design and delivery, this type of gene therapy may someday prove useful for therapy of a variety of human diseases. 

The objective of this chapter is to present an overview of peptide-based gene delivery systems. Some excellent reviews have been written recently on this topic, so we shall only do a summary of fusogenic peptides and then we wih present our recent data. We will particularly focus on the recent progress made concerning low molecular peptide-based gene delivery systems. We wih also attempt to make readers aware of the conceptual and experimental aspects of peptide-based gene delivery system design. 

Table 17.2 Guidelines for design of nontoxic poly cationic polymers for gene delivery...

Karmali PP, Kumar VV, Chaudhuri A (2004) Design, syntheses and in vitro gene delivery efficacies of novel mono-, di- and trilysinated cationic lipids a structure-activity investigation. J Med Chem 47 2123-2132... 

The search for an efficient and non-toxic gene transfection vector has led to the design and synthesis of a great variety of macromolecular scaffolds. An extensive analysis of the key features for the efficient and safe delivery of genes in vivo and in vitro has led to the conclusion that hyperbranched polymers are potential candidates for further development. In this chapter we have presented a detailed analysis of the different hyperbranched polymer scaffolds commonly used in gene delivery applications. Several structural modifications toward the development of an optimal gene vector have been analyzed. 

Murata J, Ohya Y, Ouchi T (1997) Design of quaternary chitosan conjugate having antennary galactose residues as a gene delivery tool. Carbohydr Polym 32(2) 105-109... 

Pack DW, Putnam D, Langer R (2000) Design of imidazole-containing endosomolytic biopolymers for gene delivery. Biotechnol Bioeng 67(2) 217-223... 

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