RNAi In Vivo: Biodistribution


Introduction of synthetic siRNA via transfection exhibits a transient alteration in gene expression for a specific gene of interest.  By synthesizing a siRNA mimic to each gene, RNAi may be utilized in a systematic approach to silence every gene in a cell, one gene at a time.  For this reason, large scale screens can aid in mechanism of action determination, pathway analysis, anti-proliferation studies, etc. by exploitation of the RNAi pathway.  Highly efficient animal siRNA delivery kits are typically nanoparticle– and liposome-based siRNA in vivo transfection reagents.

In a typical animal study, post-treatment tissue samples are collected from the animal for RNA isolation and gene quantitation (e.g. qRT-PCR or western blot).  Resection of multiple tissues enables the researcher to grasp a view of the efficacy and global biodistribution of their therapeutic compound.  qRT-PCR assays designed to detect the delivered siRNA or miRNA show delivery of the active pharmaceutical ingredient (API) to tissues throughout the body of the animal.  However, keep in mind that delivery to a tissue does not necessarily mean the delivered cargo is active; changes in target gene expression should be monitored as well.

Biomarker discovery refers to the use of protein, mRNA, or miRNA samples to determine differential expression of disease versus normal cells, or perhaps a treated versus non-treated sample.  With the advent of high throughput sequencing and other quantitative tools, pharmaceutical companies are using these new technologies to find new druggable targets, as well as determining ways to increase efficacy of current and orphan drugs.  The discovery of biomarkers is another service laboratories are offering assistance with.