Gene therapy

Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics. Voutetakis, A. et al. Proc. Natl Acad. Sci. USA 101, 3053–3058 (2004)

The authors show that salivary glands have potential as a target tissue for gene therapy, and could circumvent the safety concerns that surround the targeting of critical-for-life organs. They administered low doses of adeno-associated virus vector-encoding human erythropoietin (hEPO) to mouse salivary glands. Encouragingly, vector DNA was only found in the target salivary glands, and the increased serum hEPO levels were stable and vector-dependent.

Technology

Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Ui-Tei K. et al. Nucleic Acids Res. 32, 936–948 (2004)

Most siRNAs simply do not do what researchers want them to do: that is, to silence genes in an effective sequence-specific fashion. Using various gene targets and cells, Kumiko Ui-Tei and colleagues systematically analysed the gene-silencing abilities of siRNAs and deduced four rules for selecting those that work in mammal and chick cells. It seems that the nucleotides that lie towards the end of the sense and antisense strands are most important to the success of siRNAs.

Statistical genetics

A general framework for analysing the genetic architecture of developmental characteristics. Wu, R. et al. Genetics 166, (in the press)

The growth of an organism is shaped by the way genes interact with each other and with the environment. The authors of the paper have developed and tested a statistical model that maps the quantitative trait loci that affect the trajectory of development and have quantified their effect; importantly, the model also measures the contribution of epistasis to growth at various stages of development.

Evolution

High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal. Aguilar, A. et al. Proc. Natl Acad. Sci. USA 27 Feb 2004 (doi:10.1073/pnas.0306582101)

Although the San Nicolas island fox is the most genetically monomorphic among sexually reproducing mammals, it has high levels of variation at MHC loci. Using a simulation, the authors show that this could arise following a severe bottleneck in the population's past, combined with unusual selection coefficients. These results have implications for conservation genetics: inbreeding in small populations of endangered species might best be minimized by preserving diverse fitness-related genes as well as neutral variation.