Bacterial Vectors for RNAi Delivery to Cancer Cells

Abstract

Difficulties with blocking many potential therapeutic cancer targets using conventional pharmacologic approaches have directed efforts to develop alternative treatment strategies. One of these, RNA interference (RNAi), carries a great potential for new gene therapeutic protocols to treat cancer in clinics. However, many physiological obstacles stand in the way of a successful and efficient delivery of RNAi effectors in target cells. As it has long been known that bacteria can specifically target tumors, it was consistent to develop gene therapeutic strategies which utilize nonpathogenic bacteria to produce and deliver therapeutic RNAi effectors into tumor cells. Two bacteria-based gene therapeutic concepts were developed for this therapeutic option, namely transkingdom RNAi (tkRNAi) and bacteria-mediated RNAi (bmRNAi). The first concept, tkRNAi, delivers RNAi effectors into target cells by invasive bacteria which themselves produce therapeutic RNA molecules. The bmRNAi technology utilizes invasive bacteria conveying RNAi effector-encoding DNA vectors which will act as a matrix for the transcription of these sequences in the target cell by the host cell's transcription machinery. Keywords: transkingdom RNAi (tkRNAi); bacteria-mediated RNAi (bmRNAi); RNA-based therapeutics; RNA interference (RNAi)