Concepts in in vivo siRNA delivery for cancer therapy

Abstract

In vivo gene silencing using RNAi plays an important role in target validation and is advancing towards the development of RNAi-based therapeutics. RNAs were thought to have just two broad functions in cells as messenger RNAs (mRNAs) and ribosomal RNAs, but recently the relevance of microRNAs is becoming more clearly understood. mRNA molecules transmit information between DNA and protein and, as such, are vital intermediaries for gene expression. Ribosomal and transfer RNAs have structural, catalytic, and information-decoding roles in the process of protein synthesis, whereas microRNAs are regulators of gene expression. This review presents the early and intriguing successes of using siRNAs for in vivo gene silencing and its use as a possible cancer therapeutics.

Figure 1. Mechanism of RNAi using siRNA molecules or siRNA expressing molecules

RNAi involves the use of specific siRNA molecules that form a complex with proteins to form the RNA-induced silencing complex (RISC). In RNAi, one siRNA molecule is capable of targeting multiple mRNA molecules.

Figure 2. In vivo siRNA delivery strategies

Delivery of siRNA in vivo can be accomplished through direct injections systemically or locally; however, direct delivery of unmodified siRNA cannot be targeted. Other methods of delivery that incorporate the use of viruses, lipids or lipid complexes have potential for use as targeted strategies.