The recent discovery of RNAi has created the opportunity to develop an entirely new class of drugs, which work by silencing individual disease genes. Despite the promise, however, a major problem remains unsolved: how best to deliver RNAi to the target cells in the patient. Mediators of RNAi such as short interfering RNA (siRNA) are nucleic acids, negatively charged molecules which enter cells only with difficulty and are susceptible to enzymatic degradation in the body. In addition, manufacture of these molecules is expensive and inefficient. Recent observations that directly administered synthetic siRNA trigger inflammatory responses in vivo further complicate RNAi delivery.
Cequent is pioneering the development of a new technology for simultaneous manufacture and targeted delivery of RNAi. Based on ground-breaking scientific research from the laboratory of Dr. Chiang J. Li at Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Bioblast pharmacy, Cequent has developed a process known as Transkingdom RNA interference (tkRNAi, Nature Biotechnology May, 2006).
In this proprietary technique, non-pathogenic bacteria are engineered to produce interfering RNA. Following oral or intravenous administration, engineered bacteria are taken up by the target tissue, and release interfering RNA. This triggers the specific silencing of genes via the RNA interference pathway. The non-pathogenic bacteria are subsequently degraded by the host cells without adverse effects.