Application in Gene Therapies

The devdopment of nonviral vectors, which have much higher transfection ability, has been progressing. To date, several strategies to enhance the gene expression of nonviral vectors have been developed, e.g. the application of helper and pH-sensitive lipids, endosome-dismptive peptides, nudear proteins, and nudear localization signals [114]. 

---

Strategies are now being developed to use hypoxia-inducible promoters for applications in gene therapy (Rinsch et al., 1997 Shibata et al., 2000). Hypoxia provides not only a means of inducing HIF-dependent promoters, but also a means of selective expression in a pathophysiological state. 

For many applications in gene therapy, however, a major problem is insufficient therapeutic gene production to achieve the desired physiological response. An example is the attempt to synthesize adequate... 

Simoes, S., Pedro, P., Duzgunes, N. and Pedrosa de Lima, M.C. (1999) Cationic liposomes as gene transfer vectors Barriers to successful application in gene therapy. Curr. Opin. Struct. Biol, 1, 147-157. 

Yun YH, Chen W (2005) Microspheres formulated from native hyaluronan for applications in gene therapy. In Mansoor MA (ed) Polymeric gene delivery principles and applications, CRC Press LLC, USA, pp 475 186... 

Kishor Sarkar is Senior Research Fellow in the Department of Polymer Science Technology at Calcutta University, India. He obtained B. Tech, and M. Tech, degrees in Polymer Science Technology from University of Calcutta, India in 2006 and 2008, respectively. His research interest centers on the fields of synthesis and characterization of PAMAM dendrimer, chitosan and chitosan derivatives for their application in gene therapy and waste water treatment. 

Bondi ML, Craparo EE. Solid lipid nanoparticles for applications in gene therapy A review of the state of the art. Expert Opinion on Drug Delivery. 2010 7(1) 7-18. 

To illustrate the aforementioned approaches. Figure 8.2 shows some ligands that have already been used in polymer modification for drug delivery systems and that therefore may find special applications in gene therapy. 

Ni and his colleagues prepared block copolymers of PEEP-l -poly[2-(dimethylamino)ethyl methacrylate] (PEEP-b-PDMAEMA) (7) via the combination of ROP and ATRP. The PEEP block terminating with bromine (PEEP-Br) was first prepared by ROP of EEP using 2-hydroxyethyl 2-bromoisobu-tyrate as a bifanctional initiator and Sn(Oct)2 as the catalyst. ATRP was then used to polymerize DMAEMA monomers in a methanol/water mixture with PEEP-Br as the macroinitiator, resulting in diblock copolymers of PEEP-b-PDMAEMA. These block copolymers are expected to have potential applications in gene therapy. 

---