itis infection^[@CR101],[@CR102]^. A current focus of several laboratories is to use miRNA or shRNA expression methods to target more than one viral transcript^[@CR103],[@CR104]^. Host proteins can also be targeted, for example siRNAs directed to diacylglycerol acyltransferase 1 (DGAT1) can reduce HCV virion production^[@CR105]^. Additionally, inhibiting the expression of the host gene product polo-like kinase 1 (PLK1) using siRNA reduces HCV replication^[@CR106]^. PLK1 inhibition is also being used in anticancer studies (see below).

Promising results have also been reported using RNAi to modify virus and host gene expression in a mouse model of genital tract herpes simplex virus 2 (HSV-2) infections^[@CR48],[@CR107]^. Lipid-complexed RNA oligonucleotides inhibited expression of the HSV-2 *UL27* and *UL29* genes and the host receptor nectin 1 (also known as PVRL1). These approaches showed efficacy in both the prevention and treatment of infection^[@CR48],[@CR107]^. The manipulation of host miRNAs to inhibit viral expression is also being explored (see further discussion below).

***RNAi for neurological disorders***. The blood--brain barrier limits access to the central nervous system (CNS) and thus the most practical manner to silence targets in neural cells is through direct injection of the RNAi trigger. As siRNAs have a short half-life, redosing using indwelling catheters would be required for chronic diseases. However, for acute illnesses or delivery to brain tumours, the short half-life of siRNAs may be desirable. By contrast, viral platforms provide lasting expression and may be ideal for chronic disorders. For example, vectors expressing therapeutic RNAi improved disease phenotypes for many months in preclinical studies in rodent models of polyglutamine repeat diseases^[@CR108],[@CR109],[@CR110],[@CR111],[@CR112],[@CR113]^, amyotrophic lateral sclerosis^[@CR114],[@CR115],[@CR116]^, Parkinson\'s disease^[@CR117]^ and Alzheimer\'s disease^[@CR118],[@CR119]^. In nonhuman primate brains, viral-vector-based s