ABSTRACT

A range of organisms (Drosophila, Caenorhabditis elegans, Neurospora, plants, and mammals) undergo sequence-speciŒc posttranscriptional gene silencing. The mechanism behind this process is a result of the normal defense against viruses and the mobilization of genetic elements (transposons; Tijsterman et al. 2002). This process is called “RNA interference” (RNAi), and results in gene silencing. On the basis of RNAi, the use of short interfering RNA (siRNA) opened a new era in the treatment of various diseases because of the following reasons. First, siRNA only interferes with

21.1 Introduction .................................................................................................. 473 21.2 siRNA and Its Environmental Effect ............................................................ 475 21.3 siRNA Delivery Systems in Cancer Treatment ............................................ 476 21.4 Chemical ModiŒcation ................................................................................. 476

21.4.1 Sugar ModiŒcations .......................................................................... 476 21.4.2 Backbone ModiŒcations ................................................................... 476 21.4.3 Base ModiŒcations ........................................................................... 477 21.4.4 Architecture ModiŒcations ............................................................... 477 21.4.5 Terminal Conjugations...................................................................... 477

21.5 Polymeric and Dendrimeric Nanocarriers .................................................... 479 21.6 Bioparticle-Like Based Delivery .................................................................. 481 21.7 Layer-by-Layer Delivery for the Protection of Carriers ............................... 482 21.8 siRNA Delivery in Cancer Treatment .......................................................... 483

21.8.1 Breast Cancer .................................................................................... 483 21.8.2 Prostate Cancer .................................................................................486 21.8.3 Lung Cancer .....................................................................................486 21.8.4 Ovarian Cancers ...............................................................................487