Transport features predict if a molecule is odorous.

In studies of vision and audition, stimuli can be chosen to span the visible or audible spectrum; in olfaction, the axes and boundaries defining the analogous odorous space are unknown. As a result, the population of olfactory space is likewise unknown, and anecdotal estimates of 10,000 odorants have endured. The journey a molecule must take to reach olfactory receptors (ORs) and produce an odor percept suggests some chemical criteria for odorants: a molecule must 1) be volatile enough to enter the air phase, 2) be nonvolatile and hydrophilic enough to sorb into the mucous layer coating the olfactory epithelium, 3) be hydrophobic enough to enter an OR binding pocket, and 4) activate at least one OR.

High-throughput analysis of mammalian olfactory receptors: measurement of receptor activation via luciferase activity.

Odorants create unique and overlapping patterns of olfactory receptor activation, allowing a family of approximately 1,000 murine and 400 human receptors to recognize thousands of odorants. Odorant ligands have been published for fewer than 6% of human receptors(1-11). This lack of data is due in part to difficulties functionally expressing these receptors in heterologous systems.

The missense of smell: functional variability in the human odorant receptor repertoire.

Humans have ~400 intact odorant receptors, but each individual has a unique set of genetic variations that lead to variation in olfactory perception. We used a heterologous assay to determine how often genetic polymorphisms in odorant receptors alter receptor function. We identified agonists for 18 odorant receptors and found that 63% of the odorant receptors we examined had polymorphisms that altered in vitro function.

RNA polymerase III can drive polycistronic expression of functional interfering RNAs designed to resemble microRNAs.

In both research and therapeutic applications of RNA interference, it is often advantageous to silence several targets simultaneously. Toward this end, several groups have developed vectors that utilize the model of endogenously encoded micro (mi) RNAs, where a single RNA polymerase II promoter can drive the expression of multiple interfering RNAs. Stronger pol III promoters have been used to drive individual short hairpin (sh) RNAs, but to date, it has been necessary to repeat the promoter in each silencing cassette to achieve multiplexed expression from a single vector.

Vector design for liver-specific expression of multiple interfering RNAs that target hepatitis B virus transcripts.

RNA interference (RNAi) is a process that can target intracellular RNAs for degradation in a highly sequence-specific manner, making it a powerful tool that is being pursued in both research and therapeutic applications. Hepatitis B virus (HBV) is a serious public health problem in need of better treatment options, and aspects of its life cycle make it an excellent target for RNAi-based therapeutics. We have designed a vector that expresses interfering RNAs that target HBV transcripts, including both viral RNA replicative intermediates and mRNAs encoding viral proteins.