A two-pronged approach

Injecting 'chimeric' RNA molecules into mice engineered to be susceptible to HIV appears to suppress the spread of the virus in these mice, researchers recently reported (Sci. Transl. Med. 1, 66ra6; 2011). This chimera could provide an alternative approach for treating HIV infection.

Ramesh Akkina of Colorado State University in Fort Collins and colleagues developed these chimeric RNA molecules by fusing two different types of RNA, both of which target HIV, together. The chimera consists of an RNA sequence called an aptamer and a small interfering RNA (siRNA). Nucleic acid aptamers are engineered to bind to specific molecular targets; the aptamer used in the chimera binds to gp120, an HIV envelope protein, and also neutralizes the virus. As part of the chimera, the gp120 aptamer also delivers an siRNA designed to target and degrade specific HIV RNAs.

The research group infected the engineered mice with HIV. They found that chimera injections provided more extensive HIV inhibition and suppressed the virus for longer than did injections of the aptamer alone. The team thinks that this therapeutic approach could potentially be used to treat patients with drug-resistant HIV. They note, however, that further studies must be carried out in animals before this therapy can be tested in humans.

Airborne prions cause disease

Challenging the common notion that prions are not airborne pathogens, researchers have reported that aerosolized prions are efficient vectors for infection transmission in mice PLoS Pathog. 7, e1001257; 2011). It was previously known that prions, misfolded proteins that are thought to cause mad cow disease and related neurodegenerative disorders, can be passed through prion-infected bodily fluid and tissue. Research on airborne spread of prions, however, was previously inconclusive.

Adriano Aguzzi of the University Hospital Zurich in Switzerland and colleagues decided to investigate whether aerosolized prions could cause infection in mice. They exposed mice to aerosolized prions that cause scrapie. All mice, except for those that were exposed to a very low concentration of prions, developed clinical scrapie and died within about 150–200 days after exposure. The mice exposed to the lowest concentration of prions appeared to develop subclinical prion infection.

The research team found that longer prion aerosol exposure times were correlated with shorter infection incubation times. Further analysis showed that, in contrast to other prion infection routes, infection from aerosolized prions is independent of the immune system. Aguzzi and colleagues note that, in light of these findings, research and diagnostic laboratories may want to rethink their prion biosafety guidelines.

MicroRNA regulates deafness

Deafness and progressive hearing loss are relatively common in the human population, yet little is known about their genetic basis. But scientists recently identified the molecular mechanism underlying deafness in a mouse model, a discovery that could lead to new treatments for progressive hearing loss.

The research team, led by Walter Marcotti from the University of Sheffield (UK) in collaboration with Karen Steel (Wellcome Trust Sanger Institute, Cambridge, UK), discovered that a mutation in a specific microRNA (miRNA) called miR-96 prevents development of the auditory sensory hair cells in mice. MiRNAs are small, noncoding RNAs that regulate protein-coding genes involved in many biological processes. miR-96 is expressed in the mammalian cochlea during development, and mutations in miR-96 are known to cause progressive hearing loss in humans and mice.

Marcotti's team studied mutant mice called diminuendo, which have a single base mutation in the gene encoding miR-96. They found that physiological development of sensory hair cells was arrested at around the day of birth in these mutants (Proc. Natl. Acad. Sci. USA doi:10.1073/pnas.1016646108; published online 18 January 2011). The results suggest that miR-96 is a “master regulator” of hair cell development.