ABSTRACT
The concept of gene therapy has now been around for several decades. The Human Genome Project brought hope of unique treatments for hitherto incurable diseases, cancers, genetic disorders, etc. The idea of introducing foreign genetic material into cells/tissues/organs to correct/treat hereditary or acquired diseases is straightforward, but the translation of this concept into clinical practice has been less than successful mainly because of two reasons: suboptimal efcacy or unacceptable toxicities, and the mode of drug delivery could be a contributor to either or both aforementioned issues. With the focus shifting from total correction to partial but effective correction with potentially lower toxicity, ribonucleic acid (RNA) interference, primarily aiming at the destruction of specic mRNA molecules, emerged as a fresh therapeutic approach in the late 1990s. Initially, researchers utilized double-stranded RNAs with more than 30 base pairs (bps) for specic gene silencing, but these were found to cause undesirable immune responses in mammalian cells. Using short 21 bp, siRNAs have now become a promising approach for the specic, posttranscriptional knockdown of disease-causing genes (Elbashir et al. 2001; Tuschl 2001). However, siRNAs possess unfavorable biopharmaceutical properties. Rapid degradation by serum
13.1 Introduction .................................................................................................. 347 13.2 Biodegradable Polymeric Carriers................................................................ 350
13.2.1 Chitosan ............................................................................................ 350 13.2.2 Polyethylenimine .............................................................................. 353 13.2.3 Poly-l-Lysine .................................................................................... 356 13.2.4 Polyurethane ..................................................................................... 358 13.2.5 Poly (dl-Lactide-co-Glycolide) ........................................................ 358 13.2.6 Cationic Star Polymers ..................................................................... 362 13.2.7 Anionic Polymers ............................................................................. 362 13.2.8 Recombinant Polymers ..................................................................... 363
13.3 Clinical Trials Involving siRNA Delivery ....................................................364 13.4 Conclusion .................................................................................................... 365 References ..............................................................................................................366
