About RNAi

RNAi Overview

RNA interference (RNAi) is a naturally occurring mechanism that inhibits gene expression in a highly selective, sequence specific way. Since its discovery little more than a decade ago, the potential of this mechanism to revolutionize medicine has sparked excitement in both the biotech and pharmaceutical industries. Its discoverers were awarded the Nobel Prize for Physiology or Medicine in 2006. RNAi is rapidly advancing both as a target validation tool in drug discovery and as a potential therapeutic.

RNAi is works through molecules called siRNA (small interfering RNA). Each specific siRNA molecule prevents the expression of a select gene by mediating the destruction of its product by a cellular apparatus called RISC (RNA induced silencing complex). The mechanism is believed to have evolved as a cellular defense against viral attack, but can be potentially directed against any target gene. Once a disease implicated gene is identified, sequence specific siRNA molecules can be designed to silence that specific gene. Synthetic siRNA is easily manufactured in therapeutic quantity and quality.

As a result of considerable investment, RNAi based therapeutics are entering the clinic with promising new treatments for diseases like macular degeneration, RSV and cancer. Calando’s RONDEL™ delivery system extends the reach of RNAi therapy by answering the new field's most pressing need — an effective and safe systemic delivery method.

RNAi In More Detail

Proteins participate in virtually every process within cells. The structure of each protein is encoded in the DNA sequence of a specific gene. To initiate the process of protein production, the cell makes a complimentary messenger RNA (mRNA) copy of the sequence of the gene that encodes for the particular protein. The mRNA, manufactured in the cell nucleus, travels into the cytoplasm of the cell where it directs the production of a protein based on the DNA sequence carried by the mRNA. When this process works uninterrupted and produces the protein, the gene is "expressed."

RNA interference (RNAi) works by directing the sequence-specific degradation of mRNA. Naturally occurring RNAi is initiated by a process in which the dsRNA is cut into smaller pieces between 21 and 25 nucleotides (nt) in length. These small interfering RNA (siRNA) associate with RNAs and several proteins to form what is known as a RNA-induced silencing complex (RISC). RISC recognizes mRNAs by matching them to the sequence of the siRNA and cleaves the target mRNAs, destroying their ability to direct the production of the specified protein.

Introduction of synthetic siRNA duplexes into cells can also trigger RNAi, resulting in transient interference of gene expression in a sequence specific manner. Thus, synthetic siRNA represents a new class of molecules with potentially significant medical applications.