Gene therapy polymer-based delivery

One difficulty associated with polymer-based gene therapy is that delivery efficiency is generally low, due to redirection of the polymer complexes to and enzymatic hydrolysis of the DNA in the lysosome, rather than release of DNA from the endosome (see Figure 2). A strategy to circumvent this is to include polymers that disrupt the endosomal membrane. This is achieved if they are active i.e. protonated) at pH 6.5 or below, but inactive (deprotonated) at pH 7.4, since the endosomal pH is around one unit lower than the cytoplasm. Hoffman, Tirrell and co-workers have developed synthetic polymers such as poly(alkyl acrylic acid)s and poly(acrylate-co-acrylic acid)s that show en-... 

This section will focus primarily on the development of nonviral vectors that are based on surfactants, phospholipids, and natural or synthetic polymers for their application to the delivery of macromolecules, mainly of genetic materials such as DNA or RNA. Development of safe and efficient vectors will expedite the success of human gene therapy, which has captured the attention recently of the public and the biomedical research community. Even though more and more new delivery vectors are being introduced into the scientific milieu with enhanced efficiency, it should be emphasized that safety always goes first, especially after the tragedy of J. Gelsinger in 1999. 

PECs are the association complexes mainly formed between oppositely charged particles (e.g., polymer-polymer, polymer-drug, polymer-surfactant, polymer-protein). These complexes are formed due to electrostatic interaction between oppositely charged polyions. This interaction avoids the use of chemical cross-linking agents that can reduce the possible toxicity and other undesirable effects of the reagents. The PECs formed between a poly acid and poly base are less affected by the pH variation of the dissolution medium. The complexation, between DNA and chitosan, has been extensively studied in the development of delivery vehicle for gene therapy and oral vaccination. 

The successful appUcation of gene therapy through DNA or siRNA transfection into the cell is still a great challenge in research. Polymer-based DNA or RNA delivery systems offer a great potential for the facilitation of cellular uptake. 

The aim of this chapter is to give a brief selective overview of typical biomedical areas where cationic polymers can be employed. The use of cationic polymers in tissue engineering is a high priority topic in this chapter and several aspects on this phenomenon are given related to this is the potential of cationic hydrogels for medical and pharmaceutical applications. The importance of cationic polymers and copolymers as non-viral vectors in gene therapy is described, as well as how micelles and vesicles based on cationic polypeptides can form nanostructures by self-assembly. The potential of cationic polymers for drug delivery applications is also elucidated. 

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